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Sample records for oxygen species overproduction

  1. Status epilepticus results in persistent overproduction of reactive oxygen species, inhibition of which is neuroprotective.

    PubMed

    Williams, S; Hamil, N; Abramov, A Y; Walker, M C; Kovac, S

    2015-09-10

    Epilepsy and seizure activity result in the generation of reactive oxygen species (ROS), which contribute to seizure-induced neuronal damage. Recent in vitro evidence indicates that NADPH oxidase contributes significantly to seizure-induced ROS. We further tested this in rat glio-neuronal cultures and in ex vivo chronic epileptic rat brain tissue using live cell-imaging techniques. Here, we show that ROS are upregulated in chronic epilepsy and that ROS production contributes to cell death, which is seen after status epilepticus (SE) and chronic seizures. Inhibition of ROS production by AEBSF, a NADPH oxidase inhibitor, markedly reduced seizure-induced cell death in the perforant path model of epilepsy. These findings demonstrate a critical role for ROS, generated by NADPH oxidase, contributing to seizure-induced cell death. These findings point to NADPH oxidase inhibition as a novel treatment strategy to prevent brain injury in SE and chronic epilepsy. PMID:26162241

  2. Does underwater rugby stimulate the over-production of reactive oxygen species?

    PubMed

    Cavas, Levent

    2005-01-01

    Antioxidant enzymes in erythrocytes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and antioxidant sex hormone oestradiol in serum and malondialdehyde (MDA) production as a marker of lipid peroxidation in erythrocytes were investigated in male and female underwater rugby (UWR) players. Results showed that except for GSH-Px activity in female players, all antioxidant enzymes increased significantly (p < 0.05) after an UWR game. It was interesting to note that while the concentration of oestradiol in female players did not change, it increased significantly (p < 0.05) in male players. Lipid peroxidation (LPO) levels in female players as well as oestradiol concentration did not change significantly (p > 0.05) whereas LPO levels in male players increased significantly (p < 0.05) compared to pre-exercise values. In conclusion, the results showed that underwater rugby can stimulate over-production of ROS and antioxidant systems and affect oestradiol levels in male players. Because of increased LPO levels observed in male players, complex antioxidant supplementation including co-factors of antioxidant enzymes such as Cu, Zn, Fe, Se and antioxidant vitamins such as vitamin C and E may be recommended to players before the UWR game. PMID:15386531

  3. Folate Deficiency Triggered Apoptosis of Synoviocytes: Role of Overproduction of Reactive Oxygen Species Generated via NADPH Oxidase/Mitochondrial Complex II and Calcium Perturbation.

    PubMed

    Hsu, Hung-Chih; Chang, Wen-Ming; Wu, Jin-Yi; Huang, Chin-Chin; Lu, Fung-Jou; Chuang, Yi-Wen; Chang, Pey-Jium; Chen, Kai-Hua; Hong, Chang-Zern; Yeh, Rang-Hui; Liu, Tsan-Zon; Chen, Ching-Hsein

    2016-01-01

    Despite a plethora of literature has documented that osteoarthritis (OA) is veritably associated with oxidative stress-mediated chondrocyte death and matrix degradation, yet the possible involvement of synoviocyte abnormality as causative factor of OA has not been thoroughly investigated. For this reason, we conduct the current studies to insight into how synoviocytes could respond to an episode of folate-deprived (FD) condition. First, when HIG-82 synoviocytes were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature mediated through FD-evoked overproduction of reactive oxygen species (ROS) and drastically released of cytosolic calcium (Ca2+) concentrations. Next, we uncovered that FD-evoked ROS overproduction could only be strongly suppressed by either mitochondrial complex II inhibitors (TTFA and carboxin) or NADPH oxidase (NOX) inhibitors (AEBSF and apocynin), but not by mitochondrial complex I inhibitor (rotenone) and mitochondrial complex III inhibitor (antimycin A). Interestingly, this selective inhibition of FD-evoked ROS by mitochondrial complex II and NOX inhibitors was found to correlate excellently with the suppression of cytosolic Ca2+ release and reduced the magnitude of the apoptotic TUNEL-positive cells. Taken together, we present the first evidence here that FD-triggered ROS overproduction in synoviocytes is originated from mitochondrial complex II and NOX. Both elevated ROS in tandem with cytosolic Ca2+ overload serve as final arbitrators for apoptotic lethality of synoviocytes cultivated under FD condition. Thus, folate supplementation may be beneficial to patients with OA. PMID:26771387

  4. Folate Deficiency Triggered Apoptosis of Synoviocytes: Role of Overproduction of Reactive Oxygen Species Generated via NADPH Oxidase/Mitochondrial Complex II and Calcium Perturbation

    PubMed Central

    Wu, Jin-Yi; Huang, Chin-Chin; Lu, Fung-Jou; Chuang, Yi-Wen; Chang, Pey-Jium; Chen, Kai-Hua; Hong, Chang-Zern; Yeh, Rang-Hui; Liu, Tsan-Zon; Chen, Ching-Hsein

    2016-01-01

    Despite a plethora of literature has documented that osteoarthritis (OA) is veritably associated with oxidative stress-mediated chondrocyte death and matrix degradation, yet the possible involvement of synoviocyte abnormality as causative factor of OA has not been thoroughly investigated. For this reason, we conduct the current studies to insight into how synoviocytes could respond to an episode of folate-deprived (FD) condition. First, when HIG-82 synoviocytes were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature mediated through FD-evoked overproduction of reactive oxygen species (ROS) and drastically released of cytosolic calcium (Ca2+) concentrations. Next, we uncovered that FD-evoked ROS overproduction could only be strongly suppressed by either mitochondrial complex II inhibitors (TTFA and carboxin) or NADPH oxidase (NOX) inhibitors (AEBSF and apocynin), but not by mitochondrial complex I inhibitor (rotenone) and mitochondrial complex III inhibitor (antimycin A). Interestingly, this selective inhibition of FD-evoked ROS by mitochondrial complex II and NOX inhibitors was found to correlate excellently with the suppression of cytosolic Ca2+ release and reduced the magnitude of the apoptotic TUNEL-positive cells. Taken together, we present the first evidence here that FD-triggered ROS overproduction in synoviocytes is originated from mitochondrial complex II and NOX. Both elevated ROS in tandem with cytosolic Ca2+ overload serve as final arbitrators for apoptotic lethality of synoviocytes cultivated under FD condition. Thus, folate supplementation may be beneficial to patients with OA. PMID:26771387

  5. Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

    PubMed Central

    2010-01-01

    Background Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ≤5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy. PMID:20925932

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

    PubMed

    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. PMID:23344905

  7. Overproduction of reactive oxygen species and activation of MAPKs are involved in apoptosis induced by PM2.5 in rat cardiac H9c2 cells.

    PubMed

    Cao, Jing; Qin, Gang; Shi, Ruizan; Bai, Feng; Yang, Guangzhao; Zhang, Mingsheng; Lv, Jiyuan

    2016-04-01

    Epidemiological studies show a positive correlation between the air levels of fine particulate matter (PM2.5 ) and cardiovascular disorders, but how PM2.5 affects cardiomyocytes has not been studied in great deal. The aim of the present study was to obtain an insight into the links among intracellular levels of reactive oxygen species (ROS), apoptosis and mitogen-activated protein kinases (MAPKs) in rat cardiac H9c2 cells exposed to PM2.5 . H9c2 cells were incubated with PM2.5 at 100-800 µg ml(-1) to evaluate the effects of PM2.5 on cell viability, cell apoptosis, intracellular levels of ROS and expression of apoptosis-related proteins as well as activation of MAPKs. PM2.5 decreased cell viability, increased the cell apoptosis rate and intracellular ROS production in a concentration-dependent manner. PM2.5 decreased the Bcl-2/Bax ratio and increased cleaved caspase-3 levels. A Western blots study showed up-regulation of phosphorylated MAPKs including extracellular signal-regulated protein kinases (ERKs), c-Jun NH2 -terminal kinases (JNKs) and p38 MAPK in the PM2.5 -treated cells. The p38 MAPK inhibitor SB239063 attenuated whereas the ERKs inhibitor PD98059 augmented the effects of PM2.5 on apoptosis and the expression of related proteins. In conclusion, PM2.5 decreases cell viability and increases apoptosis by enhancing intracellular ROS production and activating the MAPKs signaling pathway in H9c2 cells. The MAPKs signaling pathway could be a new promising target for clinical therapeutic strategies against PM2.5 -induced cardiac injury. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26472149

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

    PubMed Central

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

    2013-01-01

    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. PMID:23344905

  9. Reactive Oxygen Species and Cellular Oxygen Sensing

    PubMed Central

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

    2008-01-01

    Many organisms activate adaptive transcriptional programs to help them cope with decreased oxygen levels, or hypoxia, in their environment. These responses are triggered by various oxygen sensing systems in bacteria, yeast and metazoans. In metazoans, the hypoxia inducible factors (HIFs) mediate the adaptive transcriptional response to hypoxia by upregulating genes involved in maintaining bioenergetic homeostasis. The HIFs in turn are regulated by HIF-specific prolyl hydroxlase activity, which is sensitive to cellular oxygen levels and other factors such as tricarboxylic acid cycle metabolites and reactive oxygen species (ROS). Establishing a role for ROS in cellular oxygen sensing has been challenging since ROS are intrinsically unstable and difficult to measure. However, recent advances in fluorescence energy transfer resonance (FRET)-based methods for measuring ROS are alleviating some of the previous difficulties associated with dyes and luminescent chemicals. In addition, new genetic models have demonstrated that functional mitochondrial electron transport and associated ROS production during hypoxia are required for HIF stabilization in mammalian cells. Current efforts are directed at how ROS mediate prolyl hydroxylase activity and hypoxic HIF stabilization. Progress in understanding this process has been enhanced by the development of the FRET-based ROS probe, an vivo prolyl hydroxylase reporter and various genetic models harboring mutations in components of the mitochondrial electron transport chain. PMID:17893032

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

    PubMed

    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. PMID:24673904

  11. Reactive oxygen species in periodontitis

    PubMed Central

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

    2013-01-01

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

  12. Reactive oxygen species in cancer

    PubMed Central

    Liou, Geou-Yarh; Storz, Peter

    2013-01-01

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

  13. Reactive Oxygen Species in Cardiovascular Disease

    PubMed Central

    Sugamura, Koichi; Keaney, John F.

    2011-01-01

    Based on the ‘free-radical theory’ of disease, researchers have been trying to elucidate the role of oxidative stress from free radicals in cardiovascular disease. Considerable data indicate that ROS and oxidative stress are important features of cardiovascular diseases including atherosclerosis, hypertension, and congestive heart failure. However, blanket strategies with antioxidants to ameliorate cardiovascular disease have not generally yielded favorable results. However, our understanding or reactive oxygen species has evolved to the point that we now realize these species have important roles in physiology as well as pathophysiology. Thus, it is overly simplistic to assume a general antioxidant strategy will yield specific effects on cardiovascular disease. Indeed, there are several sources of reactive oxygen species that are known to be active in the cardiovascular system. This review will address our understanding of reactive oxygen species sources in cardiovascular disease and both animal and human data defining how reactive oxygen species contribute to physiology and pathology. PMID:21627987

  14. Rosacea, Reactive Oxygen Species, and Azelaic Acid

    PubMed Central

    2009-01-01

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

  15. Reactive oxygen species formed in organic lithium-oxygen batteries.

    PubMed

    Schwager, Patrick; Dongmo, Saustin; Fenske, Daniela; Wittstock, Gunther

    2016-04-20

    Li-oxygen batteries with organic electrolytes are of general interest because of their theoretically high gravimetric energy density. Among the great challenges for this storage technology is the generation of reactive oxygen species such as superoxides and peroxides that may react with the organic solvent molecules and other cell components. The generation of such species has been assumed to occur during the charging reaction. Here we show that superoxide is formed also during the discharge reaction in lithium ion-containing dimethyl sulfoxide electrolytes and is released into the solution. This is shown independently by fluorescence microscopy after reaction with the selective reagent 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole and by local detection using a microelectrode of a scanning electrochemcial microscope positioned in a defined distance of 10 to 90 μm above the gas diffusion electrode. PMID:26911793

  16. Mitochondrial formation of reactive oxygen species

    PubMed Central

    Turrens, Julio F

    2003-01-01

    The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2−•). Even though O2−• is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants. PMID:14561818

  17. Superoxide Dismutases and Reactive Oxygen Species

    SciTech Connect

    Cabelli, D.E.

    2011-01-01

    The 'free radical theory' of aging was introduced over a half-century ago. In this theory, much of the deleterious effects of aging were attributed to the cumulative buildup of damage from reactive oxygen species. When discussing reactive oxygen species (ROS) in aerobic systems, both superoxide radicals (O{sub 2}{sup -}) and superoxide dismutases (SODs) are considered to play prominent roles. O{sub 2}{sup -} is formed by attachment of the electron to oxygen (O{sub 2}) that is present in tens to hundreds of micromolar concentration in vivo. SODs are enzymes that serve to eliminate O{sub 2}{sup -} by rapidly converting it to O{sub 2} and hydrogen peroxide (H{sub 2}O{sub 2}). Both the radical and the enzyme will be discussed with the focus on the systems that are present in humans.

  18. Formation and Detoxification of Reactive Oxygen Species

    ERIC Educational Resources Information Center

    Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

    2004-01-01

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

  19. Formation and Detoxification of Reactive Oxygen Species

    ERIC Educational Resources Information Center

    Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

    2004-01-01

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

  20. Signal transduction by reactive oxygen species

    PubMed Central

    2011-01-01

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

  1. Senescence, Stress, and Reactive Oxygen Species

    PubMed Central

    Jajic, Ivan; Sarna, Tadeusz; Strzalka, Kazimierz

    2015-01-01

    Generation of reactive oxygen species (ROS) is one of the earliest responses of plant cells to various biotic and abiotic stresses. ROS are capable of inducing cellular damage by oxidation of proteins, inactivation of enzymes, alterations in the gene expression, and decomposition of biomembranes. On the other hand, they also have a signaling role and changes in production of ROS can act as signals that change the transcription of genes that favor the acclimation of plants to abiotic stresses. Among the ROS, it is believed that H2O2 causes the largest changes in the levels of gene expression in plants. A wide range of plant responses has been found to be triggered by H2O2 such as acclimation to drought, photooxidative stress, and induction of senescence. Our knowledge on signaling roles of singlet oxygen (1O2) has been limited by its short lifetime, but recent experiments with a flu mutant demonstrated that singlet oxygen does not act primarily as a toxin but rather as a signal that activates several stress-response pathways. In this review we summarize the latest progress on the signaling roles of ROS during senescence and abiotic stresses and we give a short overview of the methods that can be used for their assessment. PMID:27135335

  2. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    PubMed Central

    2014-01-01

    Calcium oxalate (CaOx) kidney stones are formed attached to Randall’s plaques (RPs) or Randall’s plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall’s plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles at the basal side. In addition endothelial cells lining the blood vessels may also become osteogenic producing membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of the RP’s is sustained by mineralization of collagen laid down as result of inflammation and fibrosis. PMID:25383321

  3. REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER

    PubMed Central

    Sreevalsan, Sandeep; Safe, Stephen

    2013-01-01

    Several agents used for treatment of colon and other cancers induce reactive oxygen species (ROS) and this plays an important role in their anticancer activities. In addition to the well-known proapoptotic effects of ROS inducers, these compounds also decrease expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and several pro-oncogenic Spregulated genes important for cancer cell proliferation, survival and metastasis. The mechanism of these responses involve ROS-dependent downregulation of microRNA-27a (miR-27a) or miR-20a (and paralogs) and induction of two Sp-repressors, ZBTB10 and ZBTB4 respectively. This pathway significantly contributes to the anticancer activity of ROS inducers and should be considered in development of drug combinations for cancer chemotherapy. PMID:25584043

  4. Reactive Oxygen Species in Health and Disease

    PubMed Central

    Alfadda, Assim A.; Sallam, Reem M.

    2012-01-01

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

  5. Downregulation of Reactive Oxygen Species in Apoptosis

    PubMed Central

    Jeong, Chul-Ho; Joo, Sang Hoon

    2016-01-01

    Generation of reactive oxygen species (ROS) by diverse anti-cancer drugs or phytochemicals has been closely related with the induction of apoptosis in cancers. Also, the downregulation of ROS by these chemicals has been found to block initiation of carcinogenesis. Therefore, modulation of ROS by phytochemicals emerges as a crucial mechanism to regulate apoptosis in cancer prevention or therapy. This review summarizes the current understanding of the selected chemical compounds and related cellular components that modulate ROS during apoptotic process. Metformin, quercetin, curcumin, vitamin C, and other compounds have been shown to downregulate ROS in the cellular apoptotic process, and some of them even induce apoptosis in cancer cells. The cellular components mediating the downregulation of ROS include nuclear factor erythroid 2-related factor 2 antioxidant signaling pathway, thioredoxin, catalase, glutathione, heme oxygenase-1, and uncoupling proteins. The present review provides information on the relationship between these compounds and the cellular components in modulating ROS in apoptotic cancer cells. PMID:27051644

  6. Reactive Oxygen Species and the Cardiovascular System

    PubMed Central

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

    2013-01-01

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

  7. Production and Consumption of Reactive Oxygen Species by Fullerenes

    EPA Science Inventory

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

  8. Influence of reactive oxygen species on the sterilization of microbes

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  9. Reactive oxygen species and redox compartmentalization

    PubMed Central

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

    2014-01-01

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

  10. Reactive oxygen species and anti-proteinases.

    PubMed

    Siddiqui, Tooba; Zia, Mohammad Khalid; Ali, Syed Saqib; Rehman, Ahmed Abdur; Ahsan, Haseeb; Khan, Fahim Halim

    2016-02-01

    Reactive oxygen species (ROS) cause damage to macromolecules such as proteins, lipids and DNA and alters their structure and function. When generated outside the cell, ROS can induce damage to anti-proteinases. Anti-proteinases are proteins that are involved in the control and regulation of proteolytic enzymes. The damage caused to anti-proteinase barrier disturbs the proteinase-anti-proteinases balance and uncontrolled proteolysis at the site of injury promotes tissue damage. Studies have shown that ROS damages anti-proteinase shield of the body by inactivating key members such as alpha-2-macroglobulin, alpha-1-antitrypsin. Hypochlorous acid inactivates α-1-antitrypsin by oxidizing a critical reactive methionine residue. Superoxide and hypochlorous acid are physiological inactivators of alpha-2-macroglobulin. The damage to anti-proteinase barrier induced by ROS is a hallmark of diseases such as atherosclerosis, emphysema and rheumatoid arthritis. Thus, understanding the behaviour of ROS-induced damage to anti-proteinases may helps us in development of strategies that could control these inflammatory reactions and diseases. PMID:26699123

  11. Reactive oxygen species enhance insulin sensitivity

    PubMed Central

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

    2010-01-01

    SUMMARY Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. In recent years it has become apparent that ROS generation in response to physiological stimuli such as insulin may also facilitate signaling by reversibly oxidizing and inhibiting protein tyrosine phosphatases (PTPs). Here we report that mice lacking one of the key enzymes involved in the elimination of physiological ROS, glutathione peroxidase 1 (Gpx1), were protected from high fat diet-induced insulin resistance. The increased insulin sensitivity in Gpx1−/− mice was attributed to insulin-induced phosphatidylinositol-3-kinase/Akt signaling and glucose uptake in muscle and could be reversed by the anti-oxidant N-acetylcysteine. Increased insulin signaling correlated with enhanced oxidation of the PTP family member PTEN, which terminates signals generated by phosphatidylinositol-3-kinase. These studies provide causal evidence for the enhancement of insulin signaling by ROS in vivo. PMID:19808019

  12. Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation

    PubMed Central

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

    2012-01-01

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

  13. Skin, Reactive Oxygen Species, and Circadian Clocks

    PubMed Central

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

    2014-01-01

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

  14. Reactive Oxygen Species in Combustion Aerosols

    NASA Astrophysics Data System (ADS)

    Balasubramanian, R.; See, S.

    2007-12-01

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

  15. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

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

    2014-01-01

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

  16. Highly reactive oxygen species: detection, formation, and possible functions.

    PubMed

    Freinbichler, Wolfhardt; Colivicchi, Maria A; Stefanini, Chiara; Bianchi, Loria; Ballini, Chiara; Misini, Bashkim; Weinberger, Peter; Linert, Wolfgang; Varešlija, Damir; Tipton, Keith F; Della Corte, Laura

    2011-06-01

    The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies. PMID:21533983

  17. Balancing the generation and elimination of reactive oxygen species

    USGS Publications Warehouse

    Rodriguez, Rusty; Redman, Regina

    2005-01-01

    Fossil records suggest that bacteria developed the ability to photosynthesize ≈3,500 million years ago (mya), initiating a very slow accumulation of atmospheric oxygen (1). Recent geochemical models suggest that atmospheric oxygen did not accumulate to levels conducive for aerobic life until 500–1,000 mya (2, 3). The oxygenation of Earth's atmosphere resulted in the emergence of aerobic organisms followed by a great diversification of biological species and the eventual evolution of humans.

  18. Autophagy protein Ulk1 promotes mitochondrial apoptosis through reactive oxygen species.

    PubMed

    Mukhopadhyay, Subhadip; Das, Durgesh Nandini; Panda, Prashanta Kumar; Sinha, Niharika; Naik, Prajna Paramita; Bissoyi, Akalabya; Pramanik, Krishna; Bhutia, Sujit Kumar

    2015-12-01

    Regardless of rapid progression in the field of autophagy, it remains a challenging task to understand the cross talk with apoptosis. In this study, we overexpressed Ulk1 in HeLa cells and evaluated the apoptosis-inducing potential of the Ulk1 gene in the presence of cisplatin. The gain of function of Ulk1 gene showed a decline in cell viability and colony formation in HeLa cells. The Ulk1-overexpressing cells showed higher apoptotic attributes by an increase in the percentage of annexin V, escalated expression of Bax/Bcl2 ratio, and caspase-9, -3/7 activities. Further, reactive oxygen species (ROS) generation was found to be much higher in HeLa-Ulk1 than in the mock group. Scavenging the ROS by N-acetyl-L-cysteine increased cell viability and colony number as well as mitochondrial membrane potential (MMP). Our data showed that Ulk1 on entering into mitochondria inhibits the manganese dismutase activity and intensifies the mitochondrial superoxide level. The Ulk1-triggered autophagy (particularly mitophagy) resulted in a fall in ATP; thus the nonmitophagic mitochondria overwork the electron-transport cycle to replenish energy demand and are inadvertently involved in ROS overproduction that led to apoptosis. In this present investigation, our results decipher a previously unrecognized perspective of apoptosis induction by a key autophagy protein Ulk1 that may contribute to identification of its tumor-suppressor properties through dissecting the connection among cellular bioenergetics, ROS, and MMP. PMID:26409225

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

    PubMed Central

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

    2013-01-01

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

  20. Lysosome-controlled efficient ROS overproduction against cancer cells with a high pH-responsive catalytic nanosystem

    NASA Astrophysics Data System (ADS)

    Fu, Jingke; Shao, Yiran; Wang, Liyao; Zhu, Yingchun

    2015-04-01

    Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests promising applications in cancer treatments.Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests promising applications in cancer treatments. Electronic supplementary information (ESI) available: Experimental section, supplementary figures and characterization of as-prepared compounds. See DOI: 10.1039/c5nr00706b

  1. [Reactive oxygen species, stress and cell death in plants].

    PubMed

    Parent, Claire; Capelli, Nicolas; Dat, James

    2008-04-01

    Plants are constantly exposed to changes in environmental conditions. During periods of stress, the cellular redox homeostasis is altered as a result of reactive oxygen species accumulation. The change in redox is responsible for the symptoms commonly observed during periods of stress and reflects the phytotoxic nature of oxygen radical accumulation. However, oxygen radicals have recently been identified as key actors in the response to stress and their role as secondary messengers is now clearly established. The identification of their role in gene regulation has allowed one to identify them as key regulators in the induction and execution of programmed cell death typically observed during developmental processes as well as during stress responses. This review presents recent advances in the characterisation of the role of reactive oxygen species in plants. PMID:18355747

  2. Comparison of two strategies for detection of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

    2014-09-01

    Photodynamic therapy (PDT) is a clinically approved treatment that was applied to oncology , dermatology, and ophthalmology. Reactive oxygen species (ROS) play a important role in the efficacy of PDT. Online monitoring of reactive oxygen species is the key to understand effect of PDT treatment. We used Fluorescence probes DPBF and luminescent probe luminal to measure the ROS in cells. And we revaluate the relationship between the amount of light and cell survival. There is strongly correlated between the amount of light and cell kill.

  3. Reactive oxygen species production by catechol stabilized copper nanoparticles

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Ahmed, Ishtiaq; Fruk, Ljiljana

    2013-11-01

    Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based linkers could generate reactive oxygen species (ROS) that can activate peroxidase enzymes and catalyze the degradation of fluorescent dye pollutants.Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based linkers could generate reactive oxygen species (ROS) that can activate peroxidase enzymes and catalyze the degradation of fluorescent dye pollutants. Electronic supplementary information (ESI) available: Details of the synthesis of dopamine linkers and Cu NPs, peroxidase activity tests, H2O2 calibration and degradation tests for resorufin, RB and MB. See DOI: 10.1039/c3nr03563h

  4. Role of reactive oxygen species in myocardial remodeling.

    PubMed

    Zhang, Min; Shah, Ajay M

    2007-03-01

    Adverse cardiac remodeling is a fundamental process in the progression to chronic heart failure. Although the mechanisms underlying cardiac remodeling are multi-factorial, a significant body of evidence points to the crucial roles of increased reactive oxygen species. This article reviews recent advances in delineating the different sources of production for reactive oxygen species (namely mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases) that may be involved in cardiac remodeling and the aspects of the remodeling process that they affect. These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling. PMID:17386182

  5. Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I.

    PubMed

    Zhang, Bo; Chu, Wei; Wei, Peng; Liu, Ying; Wei, Taotao

    2015-12-01

    Xanthohumol is a prenylflavonoid extracted from hops (Humulus lupulus). It possesses anti-cancer and anti-inflammatory activities in vitro and in vivo, and offers therapeutic benefits for treatment of metabolic syndromes. However, the precise mechanisms underlying its pharmacological effects remain to be elucidated, together with its cellular target. Here, we provide evidence that xanthohumol directly interacts with the mitochondrial electron transfer chain complex I (NADH dehydrogenase), inhibits the oxidative phosphorylation, triggers the production of reactive oxygen species, and induces apoptosis. In addition, we show that as a result of the inhibition of the mitochondrial oxidative phosphorylation, xanthohumol exposure causes a rapid decrease of mitochondrial transmembrane potential. Furthermore, we showed that xanthohumol up-regulates the glycolytic capacity in cells, and thus compensates cellular ATP generation. Dissection of the multiple steps of aerobic respiration by extracellular flux assays revealed that xanthohumol specifically inhibits the activity of mitochondrial complex I, but had little effect on that of complex II, III and IV. Inhibition of complex I by xanthohumol caused the overproduction of reactive oxygen species, which are responsible for the induction of apoptosis in cancer cells. We also found that isoxanthohumol, the structural isomer of xanthohumol, is inactive to cells, suggesting that the reactive 2-hydroxyl group of xanthohumol is crucial for its targeting to the mitochondrial complex I. Together, the remodeling of cell metabolism revealed here has therapeutic potential for the use of xanthohumol. PMID:26453927

  6. Concerns in the application of fluorescent probes DCDHF-DA, DHR 123 and DHE to measure reactive oxygen species in vitro.

    PubMed

    Yazdani, Mazyar

    2015-12-25

    Reactive oxygen species (ROS) are formed in biological systems by partial reduction of molecular oxygen. The essential role of ROS in maintaining physiological health may be corrupted into oxidative stress by their overproduction or the exhaustion of antioxidant mechanisms. Many studies covering a broad range of methodologies have investigated ROS production and their toxic mechanisms of action. Of these methodologies, fluorometry has been among the preferred techniques. Three frequently used fluorescent probes for in vitro studies are 2',7'-dichlorodihydrofluorescein diacetate (DCDHF-DA), Dihydrorhodamine 123 (DHR 123) and Dihydroethidium (DHE). Apart from the unavoidable limitations of auto-oxidation, photo-oxidation and photo-conversion, there are also concerns relating to protocol modification for the improved monitoring of ROS. This paper aims to highlight such contributing factors, including cell culture conditions and the characteristics of individual fluorescent probes in the utilization of these selected probes in in vitro systems. PMID:26318276

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

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  8. Role of reactive oxygen species in low level light therapy

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  9. BIOMONITORING OF REACTIVE OXYGEN SPECIES IN BIOLOGICAL FLUIDS

    EPA Science Inventory

    Elevated levels of reactive oxygen species (ROS) are associated with several disease processes in humans, including cancer, asthma, diabetes, and cardiac disease. We have explored whether ROS can be measured directly in human fluids, and their value as a biomarker of exposure an...

  10. A role for reactive oxygen species in postharvest biocontrol

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Adipose dysfunction, interaction of reactive oxygen species, and inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This American Society for Nutrition sponsored symposium summary contains information about the symposium focus and the general content of speaker presentation. The focus of the symposium was to delineate the significance of obesity-associated reactive oxygen species (ROS), inflammation, and adipose ...

  12. Generation of reactive oxygen species by leukocytes of Prochilodus lineatus.

    PubMed

    de Faria, Marcos Tucunduva; Cury-Boaventura, Maria Fernanda; Lopes, Lucia Rossetti; da Silva, José Roberto Machado Cunha

    2014-04-01

    Prochilodus lineatus (curimbatá), from the Procholodontidae family, is a Brazilian freshwater fish, which is important commercially, nutritionally and ecologically. It is encountered in the Rio da Prata Bay in Southern South America. Studies on the immune system of this fish are scarce, but the physiological mechanisms of the species are analogous to those of other vertebrates. Thus, this work discusses the present study, which correlates P. lineatus leukocytes and the generation of reactive oxygen species after modulatory stimuli. Leukocytes were characterized by light and electron transmission microscopy and investigated by the generation of H2O2 and O2 (-), using phenol red, flow-cytometry and electron transmission histochemistry. The study determined that monocytes and neutrophils are the main cells responsible for generating O2 after stimulation with phorbol myristate acetate. Superoxide dismutase successfully inhibited the generation of reactive oxygen species in neutrophils and monocytes, but stimulated generation when in association with phorbol myristate acetate. Fish leukocyte samples from P. lineatus showed cross-reactivity with antibodies directed against human NADPH-oxidase antibody subunits (p47(phox) and p67(phox)). Thus, catalase enhanced the presence of p47(phox). Neutrophil mitochondria were shown to be generators of H2O2 (charged by cerium precipitate), being enlarged and changing their format. The present study contributes to a better understanding of the respiratory burst pathways in this species and suggests mitochondria as the organelle responsible for generation of reactive oxygen species. PMID:24068363

  13. The formation of metal--oxygen species at low temperatures

    SciTech Connect

    Qiu, S.L.; Lin, C.L.; Chen, J.; Strongin, M. )

    1990-05-01

    The interaction of solid molecular oxygen with Li, Cs, K, La, Ag, Cu, and Ba has been studied at 35 K or below using photoemission. A feature near 535 eV in the O 1{ital s} core-level spectra was observed when Li, Cs, K, and La were deposited on solid oxygen. This feature was identified with one electron being donated to an oxygen molecule, i.e., the superoxide species, which as far as we know has not been previously reported for La and Li. A feature at about 531.5--533 eV was identified as a peroxide species where two electrons were donated to an oxygen molecule. Finally, features at about 528--530.5 eV were identified as oxide phases where the molecular oxygen was dissociated into atomic O with formal oxidation state of {minus}2. These identifications are crucial in the determinations of the exotic features in the x-ray photoelectron spectroscopy (XPS) O 1{ital s} spectra of the high {ital T}{sub {ital c}} superconductors.

  14. Properties of reactive oxygen species by quantum Monte Carlo

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  15. Properties of reactive oxygen species by quantum Monte Carlo.

    PubMed

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

    2014-07-01

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

  16. Properties of reactive oxygen species by quantum Monte Carlo

    SciTech Connect

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

    2014-07-07

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

  17. Chemical pathway analysis of Titan's upper atmosphere: Oxygen species

    NASA Astrophysics Data System (ADS)

    Stock, J. W.; Lara, L. M.; Lehmann, R.

    2014-04-01

    CO, CO2, and H2O are the only oxygen bearing species in Titan's atmosphere which have been clearly detected so far. Their abundances are controlled by the interaction of external and internal sources, photochemistry and condensation. In this contribution, we determine all significant chemical pathways responsible for the production and consumption of CO, CO2, and H2O. Furthermore, we investigate the effects of different oxygen sources on the efficiencies of the pathways. In order to achieve this, we apply a unique algorithm, called the Pathway Analysis Program - PAP to the results of a 1D photochemical model of Titan's atmosphere.

  18. Reactive oxygen species generation and signaling in plants

    PubMed Central

    Tripathy, Baishnab Charan; Oelmüller, Ralf

    2012-01-01

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

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

    EPA Science Inventory

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

    Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Rece...

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

    EPA Science Inventory

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

    Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). R...

  1. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species.

    PubMed

    Amaral, Sandra; Oliveira, Paulo J; Ramalho-Santos, João

    2008-02-01

    Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested. In fact, maternal diabetes during pregnancy is associated with an increased risk of complications in the offspring, such as altered fetal growth, polyhydramnios, fetal loss and congenital malformations. In addition, hypocalemia and reduced bone mineral content are found in neonates of diabetic mothers. Abnormalities in gametogenesis and sexual function have also been documented in animal models for both types of Diabetes, which thus constitute an important research tool to both study the effects of the disease, and to test novel therapeutical interventions. Because sexuality and fertility are important aspects in the lives of individuals and couples, and considering that over 124 million individuals worldwide suffer from Diabetes, this review highlights the impact of Diabetes and associated oxidative stress on sexual function. PMID:18220695

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    Background Formaldehyde (FA) induces neurotoxicity by overproduction of intracellular reactive oxygen species (ROS). Increasing studies have shown that hydrogen sulfide (H2S), an endogenous gastransmitter, protects nerve cells against oxidative stress by its antioxidant effect. It has been shown that overproduction of nitric oxide (NO) inhibits the activity of cystathionine-beta-synthase (CBS), the predominant H2S-generating enzyme in the central nervous system. Objective We hypothesize that FA-caused neurotoxicity involves the deficiency of this endogenous protective antioxidant gas, which results from excessive generation of NO. The aim of this study is to evaluate whether FA disturbs H2S synthesis in PC12 cells, and whether this disturbance is associated with overproduction of NO. Principal Findings We showed that exposure of PC12 cells to FA causes reduction of viability, inhibition of CBS expression, decrease of endogenous H2S production, and NO production. CBS silencing deteriorates FA-induced decreases in endogenous H2S generation, neurotoxicity, and intracellular ROS accumulation in PC12 cells; while ADMA, a specific inhibitor of NOS significantly attenuates FA-induced decreases in endogenous H2S generation, neurotoxicity, and intracellular ROS accumulation in PC12 cells. Conclusion/Significance Our data indicate that FA induces neurotoxicity by inhibiting the generation of H2S through excess of NO and suggest that strategies to manipulate endogenous H2S could open a suitable novel therapeutic avenue for FA-induced neurotoxicity. PMID:23359814

  4. Lysosome-controlled efficient ROS overproduction against cancer cells with a high pH-responsive catalytic nanosystem.

    PubMed

    Fu, Jingke; Shao, Yiran; Wang, Liyao; Zhu, Yingchun

    2015-04-28

    Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests promising applications in cancer treatments. PMID:25813671

  5. Reactive oxygen species: Reactions and detection from photosynthetic tissues.

    PubMed

    Mattila, Heta; Khorobrykh, Sergey; Havurinne, Vesa; Tyystjärvi, Esa

    2015-11-01

    Reactive oxygen species (ROS) have long been recognized as compounds with dual roles. They cause cellular damage by reacting with biomolecules but they also function as agents of cellular signaling. Several different oxygen-containing compounds are classified as ROS because they react, at least with certain partners, more rapidly than ground-state molecular oxygen or because they are known to have biological effects. The present review describes the typical reactions of the most important ROS. The reactions are the basis for both the detection methods and for prediction of reactions between ROS and biomolecules. Chemical and physical methods used for detection, visualization and quantification of ROS from plants, algae and cyanobacteria will be reviewed. The main focus will be on photosynthetic tissues, and limitations of the methods will be discussed. PMID:26498710

  6. HIV-1, Reactive Oxygen Species and Vascular Complications

    PubMed Central

    Porter, Kristi M.; Sutliff, Roy L.

    2012-01-01

    Over 1 million people in the United States and 33 million individuals worldwide suffer from HIV/AIDS. Since its discovery, HIV/AIDS has been associated with an increased susceptibility to opportunistic infection due to immune dysfunction. Highly active antiretroviral therapies (HAART) restore immune function and, as a result, people infected with HIV-1 are living longer. This improved survival of HIV-1 patients has revealed a previously unrecognized risk of developing vascular complications, such as atherosclerosis and pulmonary hypertension. The mechanisms underlying these HIV-associated vascular disorders are poorly understood. However, HIV-induced elevations in reactive oxygen species, including superoxide and hydrogen peroxide, may contribute to vascular disease development and progression by altering cell function and redox-sensitive signaling pathways. In this review, we summarize the clinical and experimental evidence demonstrating HIV- and HIV antiretroviral therapy-induced alterations in reactive oxygen species (ROS) and how these effects likely contribute to vascular dysfunction and disease. PMID:22564529

  7. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    PubMed Central

    Bolisetty, Subhashini; Jaimes, Edgar A.

    2013-01-01

    The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites by mitochondria and other cellular compartments. However, this dogma was challenged when these species were demonstrated to modulate cellular responses through altering signaling pathways. In fact, since this discovery of a dichotomous role of reactive species in immune function and signal transduction, research in this field grew at an exponential pace and the pursuit for mechanisms involved began. Due to a significant number of review articles present on the reactive species mediated cell death, we have focused on emerging novel pathways such as autophagy, signaling and maintenance of the mitochondrial network. Despite its role in several processes, increased reactive species generation has been associated with the origin and pathogenesis of a plethora of diseases. While it is tempting to speculate that anti-oxidant therapy would protect against these disorders, growing evidence suggests that this may not be true. This further supports our belief that these reactive species play a fundamental role in maintenance of cellular and tissue homeostasis. PMID:23528859

  8. Heavy-metal-induced reactive oxygen species: phytotoxicity and physicochemical changes in plants.

    PubMed

    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 biomolecules. Heavy-metal-induced ROS cause lipid peroxidation, membrane dismantling and damage to DNA, protein and carbohydrates. Plants have very well-organized defense systems, consisting of enzymatic and non-enzymatic antioxidation processes. The primary defense mechanism for heavy metal detoxification is the reduced absorption of these metals into plants or their sequestration in root cells.Secondary heavy metal tolerance mechanisms include activation of antioxidant enzymes and the binding of heavy metals by phytochelatins, glutathione and amino acids. These defense systems work in combination to manage the cascades of oxidative stress and to defend plant cells from the toxic effects of ROS.In this review, we summarized the biochemiCal processes involved in the over production of ROS as an aftermath to heavy metal exposure. We also described the ROS scavenging process that is associated with the antioxidant defense machinery.Despite considerable progress in understanding the biochemistry of ROS overproduction and scavenging, we still lack in-depth studies on the parameters associated with heavy metal exclusion and tolerance capacity of plants. For example, data about the role of glutathione-glutaredoxin-thioredoxin system in ROS detoxification in plant cells are scarce. Moreover, how ROS mediate glutathionylation (redox signalling)is still not completely understood. Similarly, induction of glutathione and phytochelatins under oxidative stress is very well reported, but it is still unexplained that some studied compounds are not involved in the detoxification mechanisms. Moreover,although the role of metal transporters and gene expression is well established for a few metals and plants, much more research is needed. Eventually, when results for more metals and plants are available, the mechanism of the biochemical and genetic basis of heavy metal detoxification in plants will be better understood. Moreover, by using recently developed genetic and biotechnological tools it may be possible to produce plants that have traits desirable for imparting heavy metal tolerance. PMID:24984833

  9. Endogenous Cytokinin Overproduction Modulates ROS Homeostasis and Decreases Salt Stress Resistance in Arabidopsis Thaliana

    PubMed Central

    Wang, Yanping; Shen, Wenzhong; Chan, Zhulong; Wu, Yan

    2015-01-01

    Cytokinins in plants are crucial for numerous biological processes, including seed germination, cell division and differentiation, floral initiation and adaptation to abiotic stresses. The salt stress can promote reactive oxygen species (ROS) production in plants which are highly toxic and ultimately results in oxidative stress. However, the correlation between endogenous cytokinin production and ROS homeostasis in responding to salt stress is poorly understood. In this study, we analyzed the correlation of overexpressing the cytokinin biosynthetic gene AtIPT8 (adenosine phosphate-isopentenyl transferase 8) and the response of salt stress in Arabidopsis. Overproduction of cytokinins, which was resulted by the inducible overexpression of AtIPT8, significantly inhibited the primary root growth and true leaf emergence, especially under the conditions of exogenous salt, glucose and mannitol treatments. Upon cytokinin overproduction, the salt stress resistance was declined, and resulted in less survival rates and chlorophyll content. Interestingly, ROS production was obviously increased with the salt treatment, accompanied by endogenously overproduced cytokinins. The activities of catalase (CAT) and superoxide dismutase (SOD), which are responsible for scavenging ROS, were also affected. Transcription profiling revealed that the differential expressions of ROS-producing and scavenging related genes, the photosynthesis-related genes and stress responsive genes were existed in transgenic plants of overproducing cytokinins. Our results suggested that broken in the homeostasis of cytokinins in plant cells could modulate the salt stress responses through a ROS-mediated regulation in Arabidopsis. PMID:26635831

  10. Production of intracellular reactive oxygen species and change of cell viability induced by atmospheric pressure plasma in normal and cancer cells

    NASA Astrophysics Data System (ADS)

    Ja Kim, Sun; Min Joh, Hea; Chung, T. H.

    2013-10-01

    The effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. Using a detection dye, the production of intracellular reactive oxygen species (ROS) was found to be increased in plasma-treated cells compared to non-treated and gas flow-treated cells. A significant overproduction of ROS and a reduction in cell viability were induced by plasma exposure on cancer cells. Normal cells were observed to be less affected by the plasma-mediated ROS, and cell viability was less changed. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as a cancer therapy.

  11. The role of reactive oxygen species in PDT efficacy

    NASA Astrophysics Data System (ADS)

    Price, Michael; Okan-Mensah, Nakaiya; Santiago, Ann Marie; Kessel, David

    2009-02-01

    While the first reactive oxygen species (ROS) formed during photodynamic therapy (PDT) is singlet molecular oxygen (1O2), other ROS are formed downstream including superoxide anion radical (•CO2 -), hydrogen peroxide (H2O2) and hydroxyl radical (•OH). In this study, we examined the role of H2O2 in the phototoxic response to PDT in murine leukemia L388 cells. Inhibition of catalase activity, a major pathway to H2O2 detoxification, led to enhanced apoptosis and cell death. Addition of exogenous catalase offered protection from phototoxicity as did chelation of Fe+2, a co-factor in •OH production from H2O2. These results indicate the H2O2 formed during PDT plays a role in PDT efficacy.

  12. Reactive oxygen species and the Antarctic macroalgal wound response.

    PubMed

    McDowell, Ruth E; Amsler, Charles D; Dickinson, Dale A; McClintock, James B; Baker, Bill J

    2014-02-01

    Reactive oxygen species (ROS) are commonly produced by algal, vascular plant, and animal cells involved in the innate immune response as cellular signals promoting defense and healing and/or as a direct defense against invading pathogens. The production of reactive species in macroalgae upon injury, however, is largely uncharacterized. In this study, we surveyed 13 species of macroalgae from the Western Antarctic Peninsula and show that the release of strong oxidants is common after macroalgal wounding. Most species released strong oxidants within 1 min of wounding and/or showed cellular accumulation of strong oxidants over an hour post-wounding. Exogenous catalase was used to show that hydrogen peroxide was a component of immediate oxidant release in one of five species, but was not responsible for the entire oxidative wound response as is common in vascular plants. The other component(s) of the oxidant cocktail released upon wounding are unknown. We were unable to detect protein nitration in extracts of four oxidant-producing species flash frozen 30 s after wounding, but a role for reactive nitrogen species such as peroxynitrite cannot be completely ruled out. Two species showed evidence for the production of a catalase-activated oxidant, a mechanism previously known only from the laboratory and from the synthetic drug isoniazid used to kill the human pathogen Mycobacterium tuberculosis. The rhodophyte Palmaria decipiens, which released strong oxidants after wounding, also produced strong oxidants upon grazing by a sympatric amphipod, suggesting that oxidants are involved in the response to grazing. PMID:26988009

  13. Oxygen limitation and thermal tolerance in two terrestrial arthropod species.

    PubMed

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

    2010-07-01

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

  14. Evidence for reactive oxygen species inducing mutations in mammalian cells.

    PubMed Central

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

    1986-01-01

    We have studied the mutagenicity (by selecting for mutants resistant to 6-thioguanine) and cytotoxicity (by determining cellular cloning efficiency) of physical and chemical agents in Chinese hamster ovary (CHO) cells, clone CHO-K1-BH4 (K1-BH4), and its radiation-hypersensitive transformant, AS52. AS52 cells contain a single functional copy of a bacterial gene, the xanthine/guanine phosphoribosyltransferase (gpt) gene instead of its mammalian equivalent, the hypoxanthine/guanine phosphoribosyltransferase (hprt) gene. We found that x-ray and neutron irradiations are equally toxic to both cell types; however, these physical agents are approximately equal to 10 times more mutagenic to AS52 cells than to K1-BH4 cells. Our earlier studies using Southern blot analysis showed that x-irradiation produces mostly or exclusively deletion mutations in both cell types. If reactive oxygen species mediate the mutagenic effects of radiations and chemicals, then radiomimetic compounds such as streptonigrin and bleomycin, which exert their biological effects via reactive oxygen species, and oxidizing compounds such as potassium superoxide and hydrogen peroxide should elicit a similar differential mutagenic response in both cell types. On the other hand, agents such as ethyl methanesulfonate, ICR 191, and UV light, which do not produce reactive oxygen species, should not elicit differential mutagenicity. Our results fulfill such predictions. The apparent hypermutability of AS52 cells probably results from a higher recovery of multilocus deletion mutants in AS52 cells than in K1-BH4 cells, rather than a higher yield of induced mutants. PMID:2432598

  15. Manganese Neurotoxicity and the Role of Reactive Oxygen Species

    PubMed Central

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

    2013-01-01

    Manganese (Mn) is an essential dietary nutrient but excess or accumulations can be toxic. Disease states, like manganism, are associated with overexposure or accumulation of Mn and are due to the production of reactive oxygen species, free radicals and toxic metabolites, alteration of mitochondrial function and ATP production and depletion of cellular antioxidant defense mechanisms. This review focuses on all of the preceding mechanisms and the scientific studies that support them as well as provides an overview of the absorption, distribution, and excretion of Mn and the stability and transport of Mn compounds in the body. PMID:23395780

  16. Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species

    PubMed Central

    Kovacic, Peter; Somanathan, Ratnasamy

    2012-01-01

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

  17. NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation

    PubMed Central

    Sela, M; Tirza, G; Ravid, O; Volovitz, I; Solodeev, I; Friedman, O; Zipori, D; Gur, E; Krelin, Y; Shani, N

    2015-01-01

    Mesenchymal stromal cells (MSCs) are multipotent and can be derived from different adult tissues including fat. Our repeated attempts to produce long-term proliferative cultures of rat abdominal adipose stem cells (aASCs) under normal oxygen concentration (21%) were unsuccessful. We set to examine the events controlling this cytostasis of aASCs and found that it resulted from overproduction of reactive oxygen species (ROS) that led to apoptosis. ROS overproduction in aASCs was accompanied by increased expression of NOX1 but not of NOX2 or NOX4. NOX family members are an important source of intracellular ROS pointing to NOX1 involvement in ROS accumulation. This was verified when aASCs that were grown under 3% oxygen conditions expanded long term, displaying reduced NOX1 expression and decreased ROS accumulation. NOX1 involvement in aASC cytostasis was reaffirmed when cells that were expanded under normoxic conditions in the presence of a specific NOX1 inhibitor, ML171, demonstrated reduced ROS accumulation, reduced apoptosis and long-term expansion. aASC expansion arrest was accompanied also by a weak fat differentiation and migratory potential, which was enhanced by NOX1 inhibition. This suggests an inhibitory role for NOX1-induced ROS overproduction on aASCs, their fat differentiation and migratory potential. In contrast to aASCs, similar cells produced from subcutaneous fat were easily expanded in normoxic cultures, exhibiting low ROS concentrations, a low number of apoptotic cells and improved fat differentiation and migration. Taken together, our results show, for the first time, that NOX1-induced ROS accumulation halts ASC expansion and reduces their differentiation and migratory potential under normoxic conditions. Importantly, this phenotype comprises a tissue-specific signature as it was evident in aASCs but not in subcutaneous ASCs. NOX-induced ROS accumulation and cytokine production by fat are part of the metabolic syndrome. The similarity of this phenomenon to aASC phenotype may indicate that they arise from similar molecular mechanisms. PMID:25880095

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

    PubMed

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

    2014-03-01

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

  19. Azoxystrobin-induced excessive reactive oxygen species (ROS) production and inhibition of photosynthesis in the unicellular green algae Chlorella vulgaris.

    PubMed

    Liu, Lei; Zhu, Bin; Wang, Gao-Xue

    2015-05-01

    This study investigated the short-term toxicity of azoxystrobin (AZ), one of strobilurins used as an effective fungicidal agent to control the Asian soybean rust, on aquatic unicellular algae Chlorella vulgaris. The median percentile inhibition concentration (IC₅₀) of AZ for C. vulgaris was found to be 510 μg L(-1). We showed that the algal cells were obviously depressed or shrunk in 300 and 600 μg L(-1) AZ treatments by using the electron microscopy. Furthermore, 19, 75, and 300 μg L(-1) AZ treatments decreased the soluble protein content and chlorophyll concentrations in C. vulgaris and altered the energy-photosynthesis-related mRNA expression levels in 48- and 96-h exposure periods. Simultaneously, our results showed that AZ could increase the total antioxidant capacity (T-AOC) level and compromise superoxide dismutase (SOD), peroxidase (POD), glutathione S transferase (GST), glutathione peroxidase (GPx) activities, and glutathione (GSH) content. These situations might render C. vulgaris more vulnerable to oxidative damage. Overall, the present study indicated that AZ might be toxic to the growth of C. vulgaris, affect energy-photosynthesis-related mRNA expressions, and induce reactive oxygen species (ROS) overproduction in C. vulgaris. PMID:25672875

  20. Galangin prevents aminoglycoside-induced ototoxicity by decreasing mitochondrial production of reactive oxygen species in mouse cochlear cultures.

    PubMed

    Kim, Ye-Ri; Kim, Min-A; Cho, Hyun-Ju; Oh, Se-Kyung; Lee, In-Kyu; Kim, Un-Kyung; Lee, Kyu-Yup

    2016-03-14

    Amikacin is a semi-synthetic aminoglycoside widely used to treat infections caused by gentamicin-resistant gram-negative organisms and nontuberculous mycobacteria. However, the use of this agent often results in ototoxicity due to the overproduction of reactive oxygen species (ROS). Galangin, a natural flavonoid, has been shown to play a protective role against mitochondrial dysfunction by reducing mitochondrial ROS production. In this study, the effect of galangin on amikacin-induced ototoxicity was examined using cultures of cochlear explants. Immunofluorescent staining showed that treatment of inner hair cells (IHCs) and outer hair cells (OHCs) with galangin significantly decreased damage induced by amikacin. Moreover, pretreatment with galangin resulted in decreased amikacin-provoked increase in ROS production in both types of hair cells by MitoSOX-red staining. Attenuation of apoptotic cell death was assessed immunohistochemically using active caspase-3 antibody and with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, compared to explants exposed to amikacin alone (P<0.05). These results indicate that galangin protects hair cells in the organ of Corti from amikacin-induced toxicity by reducing the production of mitochondrial ROS. The results of this study suggest that galangin can potentially be used as an antioxidant and antiapoptotic agent to prevent hearing loss caused by aminoglycoside induced-oxidative stress. PMID:26778349

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

    PubMed Central

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

    2015-01-01

    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. PMID:25670736

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

    PubMed

    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. PMID:25670736

  3. Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species

    PubMed Central

    Widlansky, Michael E.

    2011-01-01

    Abstract Mitochondria are well known for their central roles in ATP production, calcium homeostasis, and heme and steroid biosynthesis. However, mitochondrial reactive oxygen species (ROS), including superoxide and hydrogen peroxide, once thought to be toxic byproducts of mitochondrial physiologic activities, have recently been recognized as important cell-signaling molecules in the vascular endothelium, where their production, conversion, and destruction are highly regulated. Mitochondrial reactive oxygen species appear to regulate important vascular homeostatic functions under basal conditions in a variety of vascular beds, where, in particular, they contribute to endothelium-dependent vasodilation. On exposure to cardiovascular risk factors, endothelial mitochondria produce excessive ROS in concert with other cellular ROS sources. Mitochondrial ROS, in this setting, act as important signaling molecules activating prothrombotic and proinflammatory pathways in the vascular endothelium, a process that initially manifests itself as endothelial dysfunction and, if persistent, may lead to the development of atherosclerotic plaques. This review concentrates on emerging appreciation of the importance of mitochondrial ROS as cell-signaling molecules in the vascular endothelium under both physiologic and pathophysiologic conditions. Future potential avenues of research in this field also are discussed. Antioxid. Redox Signal. 15, 1517–1530. PMID:21194353

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

    PubMed Central

    Kohno, Masahiro

    2010-01-01

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

  5. Control of root growth and development by reactive oxygen species.

    PubMed

    Tsukagoshi, Hironaka

    2016-02-01

    Reactive oxygen species (ROS) are relatively simple molecules that exist within cells growing in aerobic conditions. ROS were originally associated with oxidative stress and seen as highly reactive molecules that are injurious to many cell components. More recently, however, the function of ROS as signal molecules in many plant cellular processes has become more evident. One of the most important functions of ROS is their role as a plant growth regulator. For example, ROS are key molecules in regulating plant root development, and as such, are comparable to plant hormones. In this review, the molecular mechanisms of ROS that are mainly associated with plant root growth are discussed. The molecular links between root growth regulation by ROS and other signals will also be briefly discussed. PMID:26724502

  6. Reactive Oxygen Species and Dopamine Receptor Function in Essential Hypertension

    PubMed Central

    Zeng, Chunyu; Villar, Van Anthony M.; Yu, Peiying; Zhou, Lin; Jose, Pedro A.

    2013-01-01

    Essential hypertension is a major risk factor for stroke, myocardial infarction, and heart and kidney failure. Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones and humoral factors. However, the mechanisms leading to impaired dopamine receptor function in hypertension states are not clear. Compelling experimental evidence indicates a role of reactive oxygen species (ROS) in hypertension, and there are increasing pieces of evidence showing that in conditions associated with oxidative stress, which is present in hypertensive states, dopamine receptor effects, such as natriuresis, diuresis, and vasodilation, are impaired. The goal of this review is to present experimental evidence that has led to the conclusion that decreased dopamine receptor function increases ROS activity and vice versa. Decreased dopamine receptor function and increased ROS production, working in concert or independent of each other, contribute to the pathogenesis of essential hypertension. PMID:19330604

  7. The Role of Reactive Oxygen Species in Microvascular Remodeling

    PubMed Central

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

    2014-01-01

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

  8. NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology

    PubMed Central

    Cave, Alison; Grieve, David; Johar, Sofian; Zhang, Min; Shah, Ajay M

    2005-01-01

    Chronic heart failure, secondary to left ventricular hypertrophy or myocardial infarction, is a condition with increasing morbidity and mortality. Although the mechanisms underlying the development and progression of this condition remain a subject of intense interest, there is now growing evidence that redox-sensitive pathways play an important role. This article focuses on the involvement of reactive oxygen species derived from a family of superoxide-generating enzymes, termed NADPH oxidases (NOXs), in the pathophysiology of ventricular hypertrophy, the accompanying interstitial fibrosis and subsequent heart failure. In particular, the apparent ability of the different NADPH oxidase isoforms to define the response of a cell to a range of physiological and pathophysiological stimuli is reviewed. If confirmed, these data would suggest that independently targeting different members of the NOX family may hold the potential for therapeutic intervention in the treatment of cardiac disease. PMID:16321803

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

    PubMed

    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. PMID:26950921

  10. Reactive oxygen species as signaling molecules in neutrophil chemotaxis

    PubMed Central

    Hattori, Hidenori; Subramanian, Kulandayan K; Sakai, Jiro

    2010-01-01

    Neutrophil chemotaxis is a critical component in innate immunity. Recently, using a small-molecule functional screening, we identified NADPHoxidase- dependent Reactive Oxygen Species (ROS) as key regulators of neutrophil chemotactic migration. Neutrophils depleted of ROS form more frequent multiple pseudopodia and lost their directionality as they migrate up a chemoattractant concentration gradient. Here, we further studied the role of ROS in neutrophil chemotaxis and found that multiple pseudopodia formation induced by NADPH inhibitor diphenyleneiodonium chloride (DPI) was more prominent in relatively shallow chemoattractant gradient. It was reported that, in shallow chemoattractant gradients, new pseudopods are usually generated when existing ones bifurcate. Directional sensing is mediated by maintaining the most accurate existing pseudopod, and destroying pseudopods facing the wrong direction by actin depolymerization. We propose that NADPH-mediated ROS production may be critical for disruption of misoriented pseudopods in chemotaxing neutrophils. Thus, inhibition of ROS production will lead to formation of multiple pseudopodia. PMID:20714413

  11. Reactive oxygen species as signaling molecules in neutrophil chemotaxis.

    PubMed

    Hattori, Hidenori; Subramanian, Kulandayan K; Sakai, Jiro; Luo, Hongbo R

    2010-05-01

    Neutrophil chemotaxis is a critical component in innate immunity. Recently, using a small-molecule functional screening, we identified NADPHoxidase- dependent Reactive Oxygen Species (ROS) as key regulators of neutrophil chemotactic migration. Neutrophils depleted of ROS form more frequent multiple pseudopodia and lost their directionality as they migrate up a chemoattractant concentration gradient. Here, we further studied the role of ROS in neutrophil chemotaxis and found that multiple pseudopodia formation induced by NADPH inhibitor diphenyleneiodonium chloride (DPI) was more prominent in relatively shallow chemoattractant gradient. It was reported that, in shallow chemoattractant gradients, new pseudopods are usually generated when existing ones bifurcate. Directional sensing is mediated by maintaining the most accurate existing pseudopod, and destroying pseudopods facing the wrong direction by actin depolymerization. We propose that NADPH-mediated ROS production may be critical for disruption of misoriented pseudopods in chemotaxing neutrophils. Thus, inhibition of ROS production will lead to formation of multiple pseudopodia. PMID:20714413

  12. Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

    PubMed Central

    Fujimoto, Chisato

    2015-01-01

    Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required. PMID:25874222

  13. Reactive Oxygen Species in Normal and Tumor Stem Cells

    PubMed Central

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

    2014-01-01

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

  14. Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation

    PubMed Central

    Sovari, Ali A.; Dudley, Samuel C.

    2012-01-01

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

  15. Reactive oxygen species and the bacterial response to lethal stress

    PubMed Central

    Zhao, Xilin; Drlica, Karl

    2014-01-01

    Bacteria are killed by a variety of lethal stressors, some of which promote a cascade of reactive oxygen species (ROS). Perturbations expected to alter ROS accumulation affect the lethal action of diverse antibacterials, leading to the hypothesis that killing by these agents can involve ROS-mediated self-destruction. Recent challenges to the hypothesis are considered, particularly with respect to complexities in assays that distinguish primary damage from the cellular response to that damage. Also considered are bifunctional factors that are protective at low stress levels but destructive at high levels. These considerations, plus new data, support an involvement of ROS in the lethal action of some antimicrobials and raise important questions concerning consumption of antioxidant dietary supplements during antimicrobial chemotherapy. PMID:25078317

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

    PubMed Central

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

    2012-01-01

    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 production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production. PMID:21865257

  17. Reactive Oxygen Species in Inflammation and Tissue Injury

    PubMed Central

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

    2014-01-01

    Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126–1167. PMID:23991888

  18. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

    PubMed

    Vallyathan, V; Shi, X; Castranova, V

    1998-10-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis. PMID:9788890

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

    NASA Astrophysics Data System (ADS)

    Tada, Dayane; Baptista, Mauricio

    2015-05-01

    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.

  20. Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy.

    PubMed

    Durantini, Andrés M; Greene, Lana E; Lincoln, Richard; Martínez, Sol R; Cosa, Gonzalo

    2016-02-01

    Here we show the design, preparation, and characterization of a dormant singlet oxygen ((1)O2) photosensitizer that is activated upon its reaction with reactive oxygen species (ROS), including (1)O2 itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer-trap molecule where the photosensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipid soluble antioxidant. Time-resolved absorption, fluorescence, and (1)O2 phosphorescence studies together with fluorescence and (1)O2 phosphorescence emission quantum yields collected on Br2B-PMHC and related bromo and iodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of (1)O2 production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resulting in ∼40-fold enhancement in (1)O2 production. The juxtaposed antioxidant (chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of the two-segment compound enable the autocatalytic, and in general ROS-mediated, activation of (1)O2 sensitization providing a chemical cue for the spatiotemporal control of (1)O2.The usefulness of this approach to selectively photoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamic inactivation of a ROS stressed Gram negative Escherichia coli strain. PMID:26789198

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

    PubMed Central

    Zheng, Jiaolin; Li, Guangze; Chen, Shuzhen; Chen, Ji; Buck, Joshua; Zhu, Yulan; Xia, Huijing; Lazartigues, Eric; Chen, Yanfang; Olson, James E.

    2014-01-01

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

  2. Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

    The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

  3. Updates of reactive oxygen species in melanoma etiology and progression

    PubMed Central

    Liu-Smith, Feng; Dellinger, Ryan; Meyskens, Frank L.

    2014-01-01

    Reactive oxygen species (ROS) play crucial roles in all aspects of melanoma development, however, the source of ROS is not well defined. In this review we summarize recent advancement in this rapidly developing field. The cellular ROS pool in melanocytes can be derived from mitochondria, melanosomes, NADPH oxidase (NOX) family enzymes, and uncoupling of nitric oxide synthase (NOS). Current evidence suggests that Nox1, Nox4 and Nox5 are expressed in melanocytic lineage. While there is no difference in Nox1 expression levels in primary and metastatic melanoma tissues, Nox4 expression is significantly higher in a subset of metastatic melanoma tumors as compared to the primary tumors; suggesting distinct and specific signals and effects for NOX family enzymes in melanoma. Targeting these NOX enzymes using specific NOX inhibitors may be effective for a subset of certain tumors. ROS also play important roles in BRAF inhibitor induced drug resistance; hence identification and blockade of the source of this ROS may be an effective way to enhance efficacy and overcome resistance. Furthermore, ROS from different sources may interact with each other and interact with reactive nitrogen species (RNS) and drive the melanomagenesis process at all stages of disease. Further understanding ROS and RNS in melanoma etiology and progression is necessary for developing new prevention and therapeutic approaches. PMID:24780245

  4. Enzymatic Production of Extracellular Reactive Oxygen Species by Marine Microorganisms

    NASA Astrophysics Data System (ADS)

    Diaz, J. M.; Andeer, P. F.; Hansel, C. M.

    2014-12-01

    Reactive oxygen species (ROS) serve as intermediates in a myriad of biogeochemically important processes, including cell signaling pathways, cellular oxidative stress responses, and the transformation of both nutrient and toxic metals such as iron and mercury. Abiotic reactions involving the photo-oxidation of organic matter were once considered the only important sources of ROS in the environment. However, the recent discovery of substantial biological ROS production in marine systems has fundamentally shifted this paradigm. Within the last few decades, marine phytoplankton, including diatoms of the genus Thalassiosira, were discovered to produce ample extracellular quantities of the ROS superoxide. Even more recently, we discovered widespread production of extracellular superoxide by phylogenetically and ecologically diverse heterotrophic bacteria at environmentally significant levels (up to 20 amol cell-1 hr-1), which has introduced the revolutionary potential for substantial "dark" cycling of ROS. Despite the profound biogeochemical importance of extracellular biogenic ROS, the cellular mechanisms underlying the production of this ROS have remained elusive. Through the development of a gel-based assay to identify extracellular ROS-producing proteins, we have recently found that enzymes typically involved in antioxidant activity also produce superoxide when molecular oxygen is the only available electron acceptor. For example, large (~3600 amino acids) heme peroxidases are involved in extracellular superoxide production by a bacterium within the widespread Roseobacter clade. In Thalassiosira spp., extracellular superoxide is produced by flavoproteins such as glutathione reductase and ferredoxin NADP+ reductase. Thus, extracellular ROS production may occur via secreted and/or cell surface enzymes that modulate between producing and degrading ROS depending on prevailing geochemical and/or ecological conditions.

  5. Mitochondria: Much ado about nothing? How dangerous is reactive oxygen species production??

    PubMed Central

    Holzerov, Elika; Prokisch, Holger

    2015-01-01

    For more than 50 years, reactive oxygen species have been considered as harmful agents, which can attack proteins, lipids or nucleic acids. In order to deal with reactive oxygen species, there is a sophisticated system developed in mitochondria to prevent possible damage. Indeed, increased reactive oxygen species levels contribute to pathomechanisms in several human diseases, either by its impaired defense system or increased production of reactive oxygen species. However, in the last two decades, the importance of reactive oxygen species in many cellular signaling pathways has been unraveled. Homeostatic levels were shown to be necessary for correct differentiation during embryonic expansion of stem cells. Although the mechanism is still not fully understood, we cannot only regard reactive oxygen species as a toxic by-product of mitochondrial respiration anymore. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. PMID:25666559

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

    PubMed Central

    McCormick, Rachel; Pearson, Timothy; Vasilaki, Aphrodite

    2016-01-01

    Regulated changes in reactive oxygen and nitrogen species (RONS) activities are important in maintaining the normal sequence and development of myogenesis. Both excessive formation and reduction in RONS have been shown to affect muscle differentiation in a negative way. Cultured cells are typically grown in 20% O2 but this is not an appropriate physiological concentration for a number of cell types, including skeletal muscle. The aim was to examine the generation of RONS in cultured skeletal muscle cells under a physiological oxygen concentration condition (6% O2) and determine the effect on muscle myogenesis. Primary mouse satellite cells were grown in 20% or 6% O2 environments and RONS activity was measured at different stages of myogenesis by real-time fluorescent microscopy using fluorescent probes with different specificities i.e. dihydroethidium (DHE), 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM DA) and 5-(and-6)-chloromethyl-2′,7′ -dichlorodihydrofluorescein diacetate (CM-DCFH-DA). 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. PMID:26827127

  7. Endophytic Bacterium-Triggered Reactive Oxygen Species Directly Increase Oxygenous Sesquiterpenoid Content and Diversity in Atractylodes lancea.

    PubMed

    Zhou, Jia-Yu; Yuan, Jie; Li, Xia; Ning, Yi-Fan; Dai, Chuan-Chao

    2015-01-01

    Oxygenous terpenoids are active components of many medicinal plants. However, current studies that have focused on enzymatic oxidation reactions cannot comprehensively clarify the mechanisms of oxygenous terpenoid synthesis and diversity. This study shows that an endophytic bacterium can trigger the generation of reactive oxygen species (ROS) that directly increase oxygenous sesquiterpenoid content and diversity in Atractylodes lancea. A. lancea is a famous but endangered Chinese medicinal plant that contains abundant oxygenous sesquiterpenoids. Geo-authentic A. lancea produces a wider range and a greater abundance of oxygenous sesquiterpenoids than the cultivated herb. Our previous studies have shown the mechanisms behind endophytic promotion of the production of sesquiterpenoid hydrocarbon scaffolds; however, how endophytes promote the formation of oxygenous sesquiterpenoids and their diversity is unclear. After colonization by Pseudomonas fluorescens ALEB7B, oxidative burst and oxygenous sesquiterpenoid accumulation in A. lancea occur synchronously. Treatment with exogenous hydrogen peroxide (H2O2) or singlet oxygen induces oxidative burst and promotes oxygenous sesquiterpenoid accumulation in planta. Conversely, pretreatment of plantlets with the ROS scavenger ascorbic acid significantly inhibits the oxidative burst and oxygenous sesquiterpenoid accumulation induced by P. fluorescens ALEB7B. Further in vitro oxidation experiments show that several oxygenous sesquiterpenoids can be obtained from direct oxidation caused by H2O2 or singlet oxygen. In summary, this study demonstrates that endophytic bacterium-triggered ROS can directly oxidize oxygen-free sesquiterpenoids and increase the oxygenous sesquiterpenoid content and diversity in A. lancea, providing a novel explanation of the mechanisms of oxygenous terpenoid synthesis in planta and an essential complementarity to enzymatic oxidation reactions. PMID:26712554

  8. Zinc oxide nanoparticles induce renal toxicity through reactive oxygen species.

    PubMed

    Xiao, Lu; Liu, Chunhua; Chen, Xiaoniao; Yang, Zhuo

    2016-04-01

    Nanoparticles of zinc oxide (ZnO NPs) are applied in many fields nowadays. Consequently, concerns have been raised about its potential harmful effects. The present study focuses on its toxic effect on podocytes and rats. In vitro study, podocytes were treated with different concentrations of ZnO NPs (10, 50 and 100 μg/ml), the viability of cells was decreased as time prolonged according to MTT assay. Meantime, flow cytometry analysis indicated that ZnO NPs induced intracellular accumulation of reactive oxygen species (ROS) and apoptosis. The measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) showed that ZnO NPs decreased SOD level and increased MDA level. Interestingly, pretreatment with N-mercaptopropionyl-glycine, known as a type of ROS scavenger, could inhibit podocyte apoptosis induced by ZnO NPs. Meantime, a loss of nephrin can be detected, which may result in a direct damage to slit diaphragms. In vivo study, adult male Wistar rats were administrated with 3mg/kg/day ZnO NPs for 5 days, body weight and kidney index were significantly reduced. In addition, ZnO NPs decreased the activity of catalase and SOD in kidney cortex in vivo. It could be concluded that ZnO NPs present toxic effect on podocytes and Wistar rats, which was related with oxidative stress. PMID:26860595

  9. Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases.

    PubMed

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Kappo, Abidemi Paul

    2015-01-01

    Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance. PMID:25850012

  10. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer.

    PubMed

    Zhang, Lun; Li, Jiahui; Zong, Liang; Chen, Xin; Chen, Ke; Jiang, Zhengdong; Nan, Ligang; Li, Xuqi; Li, Wei; Shan, Tao; Ma, Qingyong; Ma, Zhenhua

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy. PMID:26881012

  11. Are reactive oxygen species always detrimental to pathogens?

    PubMed

    Paiva, Claudia N; Bozza, Marcelo T

    2014-02-20

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

  12. Reactive oxygen species in cancer, too much or too little?

    PubMed

    Lu, Fuxiong

    2007-01-01

    It is widely accepted that increased levels of reactive oxygen species (ROS) contribute to carcinogenesis. However, this claim has not been confirmed by experiments. On the contrary, a growing number of studies clearly demonstrate that ROS are normal cellular signals and induce cell differentiation and apoptosis, the opposite processes to cancer, which is dedifferentiated. Thus, it is hypothesized here that decreased levels of ROS may lead to cancer development, which is supported by following observations: (1) the fast-growing tumor produces ROS at a rate only one-third of the rate found with the control liver mitochondria; (2) the reduction in tumor mitochondrial content indicates low level of ROS production; (3) the low levels of manganese superoxide dismutase in tumor mitochondria also indicate decreased production of ROS, because the enzyme activity is induced by ROS; (4) lipid peroxidation capacity was decreased in human colon carcinomas and Yoshida hepatomas; (5) low levels of lipid peroxidation de-inhibit glucose-6-phosphate dehydrogenase, whose activity is always increased in a variety of cancers without exception. Clarification of real role of ROS in cancer may shed light on the understanding of how impairment of mitochondria leads to malignant transformation of normal cells, and offer new types of strategies for cancer prevention and therapy. PMID:17509774

  13. Reactive oxygen species in cancer, too much or too little?

    TOXLINE Toxicology Bibliographic Information

    Lu F

    2007-01-01

    It is widely accepted that increased levels of reactive oxygen species (ROS) contribute to carcinogenesis. However, this claim has not been confirmed by experiments. On the contrary, a growing number of studies clearly demonstrate that ROS are normal cellular signals and induce cell differentiation and apoptosis, the opposite processes to cancer, which is dedifferentiated. Thus, it is hypothesized here that decreased levels of ROS may lead to cancer development, which is supported by following observations: (1) the fast-growing tumor produces ROS at a rate only one-third of the rate found with the control liver mitochondria; (2) the reduction in tumor mitochondrial content indicates low level of ROS production; (3) the low levels of manganese superoxide dismutase in tumor mitochondria also indicate decreased production of ROS, because the enzyme activity is induced by ROS; (4) lipid peroxidation capacity was decreased in human colon carcinomas and Yoshida hepatomas; (5) low levels of lipid peroxidation de-inhibit glucose-6-phosphate dehydrogenase, whose activity is always increased in a variety of cancers without exception. Clarification of real role of ROS in cancer may shed light on the understanding of how impairment of mitochondria leads to malignant transformation of normal cells, and offer new types of strategies for cancer prevention and therapy.

  14. Mitochondrial signaling in the vascular endothelium: beyond reactive oxygen species.

    PubMed

    Kadlec, Andrew O; Beyer, Andreas M; Ait-Aissa, Karima; Gutterman, David D

    2016-05-01

    Traditionally, the mitochondria have been viewed as the cell's powerhouse, producing energy in the form of ATP. As a byproduct of ATP formation, the mitochondrial electron transport chain produces substantial amounts of reactive oxygen species (ROS). First thought to be toxic, recent literature indicates an important signaling function for mitochondria-derived ROS, especially in relation to cardiovascular disease pathogenesis. This has spawned an evolution to a more contemporary view of mitochondrial function as a dynamic organelle involved in key regulatory and cell survival processes. Beyond ROS, recent studies have identified a host of mitochondria-linked factors that influence the cellular and extracellular environments, including mitochondria-derived peptides, mitochondria-localized proteins, and the mitochondrial genome itself. Interestingly, many of these factors help orchestrate ROS homeostasis and ROS-related signaling. The paradigm defining the role of mitochondria in the vasculature needs to be updated yet again to include these key signaling factors, which serves as the focus of the current review. In describing these novel signaling factors, we pay specific attention to their influence on endothelial homeostasis. Therapies targeting these pathways are discussed, as are emerging research directions. PMID:26992928

  15. Mitochondrial reactive oxygen species in cell death signaling.

    PubMed

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

    2002-01-01

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

  16. Tamoxifen reduces fat mass by boosting reactive oxygen species

    PubMed Central

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

    2015-01-01

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

  17. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases

    PubMed Central

    He, Feng; Zuo, Li

    2015-01-01

    Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. PMID:26610475

  18. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases.

    PubMed

    He, Feng; Zuo, Li

    2015-01-01

    Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. PMID:26610475

  19. Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species

    PubMed Central

    Moon, Ho-Jin; Kim, Sung Eun; Yun, Young Pil; Hwang, Yu-Shik; Bang, Jae Beum

    2011-01-01

    Osteoclasts, together with osteoblasts, control the amount of bone tissue and regulate bone remodeling. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. Reactive oxygen species (ROS) acts as a signal mediator in osteoclast differentiation. Simvastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A, is a hypolipidemic drug which is known to affect bone metabolism and suppresses osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated NF-κB, protein kinases B (AKT), mitogen-activated protein kinases signaling pathways such as c-JUN N-terminal kinases, p38 MAP kinases as well as extracellular signal-regulated kinase. Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Together, these results indicate that simvastatin acts as an osteoclastogenesis inhibitor through suppression of ROS-mediated signaling pathways. This indicates that simvastatin has potential usefulness for osteoporosis and pathological bone resorption. PMID:21832867

  20. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis

    PubMed Central

    Dan Dunn, Joe; Alvarez, Luis AJ; Zhang, Xuezhi; Soldati, Thierry

    2015-01-01

    Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes as NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted by-products of oxidative metabolism. Increasing evidence indicates that mtROS have been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria. PMID:26432659

  1. Pharmacological modulation of reactive oxygen species in cancer treatment.

    PubMed

    Ribas, Judit; Mattiolo, Paolo; Boix, Jacint

    2015-01-01

    Aerobic metabolism of mammalian cells leads to the generation of reactive oxygen species (ROS). To cope with this toxicity, evolution provided cells with effective antioxidant systems like glutathione. Current anticancer therapies focus on the cancer dependence on oncogenes and non-oncogenes. Tumors trigger mechanisms to circumvent the oncogenic stress and to escape cell death. In this context we have studied 2-phenylethinesulfoxamine (PES), which disables the cell protective mechanisms to confront the proteotoxicity of damaged and unfolded proteins. Proteotoxic stress is increased in tumor cells, thus providing an explanation for the anticancer selectivity of PES. In addition, we have found that PES induces a severe oxidative stress and the activation of p53. The reduction of the cell content in glutathione by means of L-buthionine-sulfoximine (BSO) synergizes with PES. In conclusion, we have found that ROS constitutes a central element in a series of positive feed-back loops in the cell. ROS, p53, proteotoxicity, autophagy and mitochondrial dynamics are interconnected with the mechanisms leading to cell death, either apoptotic or necrotic. This network of interactions provides multiple targets for drug discovery and development in cancer. PMID:25395102

  2. Reactive oxygen species delay control of lymphocytic choriomeningitis virus

    PubMed Central

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

    2013-01-01

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

  3. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    PubMed Central

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy. PMID:26881012

  4. Reactive oxygen species: players in the cardiovascular effects of testosterone.

    PubMed

    Tostes, Rita C; Carneiro, Fernando S; Carvalho, Maria Helena C; Reckelhoff, Jane F

    2016-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

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

    SciTech Connect

    Lee, Boram; Kim, Ki Hyun; Jung, Hye Jin; Kwon, Ho Jeong

    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.

  6. Reactive Oxygen Species and the Brain in Sleep Apnea

    PubMed Central

    Wang, Yang; Zhang, Shelley XL; Gozal, David

    2010-01-01

    Rodents exposed to intermittent hypoxia (IH), a model of obstructive sleep apnea (OSA), manifest impaired learning and memory and somnolence. Increased levels of reactive oxygen species (ROS), oxidative tissue damage, and apoptotic neuronal cell death are associated with the presence of IH-induced CNS dysfunction. Furthermore, treatment with antioxidants or overexpression of antioxidant enzymes is neuroprotective during IH. These findings mimic clinical cases of OSA and suggest that ROS may play a key causal role in OSA-induced neuropathology. Controlled production of ROS occurs in multiple subcellular compartments of normal cells and de-regulation of such processes may result in excessive ROS production. The mitochondrial electron transport chain, especially complexes I and III, and the NADPH oxidase in the cellular membrane are the two main sources of ROS in brain cells, although other systems, including xanthine oxidase, phospholipase A2, lipoxygenase, cyclooxygenase, and cytochrome P450, may all play a role. The initial evidence for NADPH oxidase and mitochondrial involvement in IH-induced ROS production and neuronal injury unquestionably warrants future research efforts. PMID:20833273

  7. Reactive oxygen species a double-edged sword for mesothelioma

    PubMed Central

    Catalani, Simona; Galati, Rossella

    2015-01-01

    It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10–15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display ‘asbestos-like’ pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review. PMID:26078352

  8. REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS

    PubMed Central

    Circu, Magdalena L.; Aw, Tak Yee

    2010-01-01

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

  9. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription

    NASA Astrophysics Data System (ADS)

    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.

  10. Hemodynamic Regulation of Reactive Oxygen Species: Implications for Vascular Diseases

    PubMed Central

    Raaz, Uwe; Toh, Ryuji; Maegdefessel, Lars; Adam, Matti; Nakagami, Futoshi; Emrich, Fabian C.; Spin, Joshua M.

    2014-01-01

    Abstract Significance: Arterial blood vessels functionally and structurally adapt to altering hemodynamic forces in order to accommodate changing needs and to provide stress homeostasis. This ability is achieved at the cellular level by converting mechanical stimulation into biochemical signals (i.e., mechanotransduction). Physiological mechanical stress helps maintain vascular structure and function, whereas pathologic or aberrant stress may impair cellular mechano-signaling, and initiate or augment cellular processes that drive disease. Recent Advances: Reactive oxygen species (ROS) may represent an intriguing class of mechanically regulated second messengers. Chronically enhanced ROS generation may be induced by adverse mechanical stresses, and is associated with a multitude of vascular diseases. Although a causal relationship has clearly been demonstrated in large numbers of animal studies, an effective ROS-modulating therapy still remains to be established by clinical studies. Critical Issues and Future Directions: This review article focuses on the role of various mechanical forces (in the form of laminar shear stress, oscillatory shear stress, or cyclic stretch) as modulators of ROS-driven signaling, and their subsequent effects on vascular biology and homeostasis, as well as on specific diseases such as arteriosclerosis, hypertension, and abdominal aortic aneurysms. Specifically, it highlights the significance of the various NADPH oxidase (NOX) isoforms as critical ROS generators in the vasculature. Directed targeting of defined components in the complex network of ROS (mechano-)signaling may represent a key for successful translation of experimental findings into clinical practice. Antioxid. Redox Signal. 20, 914–928. PMID:23879326

  11. Are Reactive Oxygen Species Always Detrimental to Pathogens?

    PubMed Central

    Bozza, Marcelo T.

    2014-01-01

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

  12. Plasmodium berghei resists killing by reactive oxygen species.

    PubMed

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

    2005-10-01

    Reactive oxygen species (ROS) are widely believed to kill malarial parasites. C57BL/6 mice injected with P. berghei inocula incubated with supraphysiological doses of NO (< or =150 microM) or with peroxynitrite (220 microM), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. Only treatment of inocula with NO doses nearing saturation (> or =1.2 mM) resulted in no detectable parasitemia in the recipients; flow cytometric analysis with a vital dye (hydroethidine) indicated that 1.5 mM NO lysed the erythrocytes rather than killing the parasites. The hemoglobin level in the inocula was about 8 muM; the hemoglobin was mainly oxyhemoglobin (oxyHb) (96%), which was converted to methemoglobin (>95%) after treatment with 150 microM NO. The concentrations of 150 microM of NO and 220 microM of peroxynitrite were far in excess of the hemoglobin concentration (approximately 8 microM), and yet no parasite killing was detected. We therefore conclude that hemoglobin protects Plasmodium parasites from ROS, but the parasite likely possesses intrinsic defense mechanisms against ROS. PMID:16177347

  13. Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species

    PubMed Central

    Harrison, David G.

    2014-01-01

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

  14. Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved?

    PubMed Central

    Görlach, Agnes; Dimova, Elitsa Y.; Petry, Andreas; Martínez-Ruiz, Antonio; Hernansanz-Agustín, Pablo; Rolo, Anabela P.; Palmeira, Carlos M.; Kietzmann, Thomas

    2015-01-01

    Within the last twenty years the view on reactive oxygen species (ROS) has changed; they are no longer only considered to be harmful but also necessary for cellular communication and homeostasis in different organisms ranging from bacteria to mammals. In the latter, ROS were shown to modulate diverse physiological processes including the regulation of growth factor signaling, the hypoxic response, inflammation and the immune response. During the last 60–100 years the life style, at least in the Western world, has changed enormously. This became obvious with an increase in caloric intake, decreased energy expenditure as well as the appearance of alcoholism and smoking; These changes were shown to contribute to generation of ROS which are, at least in part, associated with the occurrence of several chronic diseases like adiposity, atherosclerosis, type II diabetes, and cancer. In this review we discuss aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues. PMID:26339717

  15. Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved?

    PubMed

    Görlach, Agnes; Dimova, Elitsa Y; Petry, Andreas; Martínez-Ruiz, Antonio; Hernansanz-Agustín, Pablo; Rolo, Anabela P; Palmeira, Carlos M; Kietzmann, Thomas

    2015-12-01

    Within the last twenty years the view on reactive oxygen species (ROS) has changed; they are no longer only considered to be harmful but also necessary for cellular communication and homeostasis in different organisms ranging from bacteria to mammals. In the latter, ROS were shown to modulate diverse physiological processes including the regulation of growth factor signaling, the hypoxic response, inflammation and the immune response. During the last 60-100 years the life style, at least in the Western world, has changed enormously. This became obvious with an increase in caloric intake, decreased energy expenditure as well as the appearance of alcoholism and smoking; These changes were shown to contribute to generation of ROS which are, at least in part, associated with the occurrence of several chronic diseases like adiposity, atherosclerosis, type II diabetes, and cancer. In this review we discuss aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues. PMID:26339717

  16. Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

    PubMed Central

    Steinhorn, Robin H.

    2014-01-01

    Abstract Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease. Antioxid. Redox Signal. 21, 1926–1942. PMID:24350610

  17. Reactive Oxygen Species, Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

    PubMed Central

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Kappo, Abidemi Paul

    2015-01-01

    Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance. PMID:25850012

  18. NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species

    PubMed Central

    Ghosh, Rajeshwary; Alajbegovic, Azra; Gomes, Aldrin V.

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD. PMID:26457127

  19. Generation of Reactive Oxygen Species from Silicon Nanowires

    PubMed Central

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

    2014-01-01

    Processing and synthesis of purified nanomaterials of diverse composition, size, and properties is an evolving process. Studies have demonstrated that some nanomaterials have potential toxic effects and have led to toxicity research focusing on nanotoxicology. About two million workers will be employed in the field of nanotechnology over the next 10 years. The unknown effects of nanomaterials create a need for research and development of techniques to identify possible toxicity. Through a cooperative effort between National Institute for Occupational Safety and Health and IBM to address possible occupational exposures, silicon-based nanowires (SiNWs) were obtained for our study. These SiNWs are anisotropic filamentary crystals of silicon, synthesized by the vapor–liquid–solid method and used in bio-sensors, gas sensors, and field effect transistors. Reactive oxygen species (ROS) can be generated when organisms are exposed to a material causing cellular responses, such as lipid peroxidation, H2O2 production, and DNA damage. SiNWs were assessed using three different in vitro environments (H2O2, RAW 264.7 cells, and rat alveolar macrophages) for ROS generation and possible toxicity identification. We used electron spin resonance, analysis of lipid peroxidation, measurement of H2O2 production, and the comet assay to assess generation of ROS from SiNW and define possible mechanisms. Our results demonstrate that SiNWs do not appear to be significant generators of free radicals. PMID:25452695

  20. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

    PubMed Central

    Vallyathan, V; Shi, X; Castranova, V

    1998-01-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9788890

  1. Reactive Oxygen Species (ROS) generation by lunar simulants

    NASA Astrophysics Data System (ADS)

    Kaur, Jasmeet; Rickman, Douglas; Schoonen, Martin A.

    2016-05-01

    The current interest in human exploration of the Moon and past experiences of Apollo astronauts has rekindled interest into the possible harmful effects of lunar dust on human health. In comparison to the Apollo-era explorations, human explorers may be weeks on the Moon, which will raise the risk of inhalation exposure. The mineralogical composition of lunar dust is well documented, but its effects on human health are not fully understood. With the aim of understanding the reactivity of dusts that may be encountered on geologically different lunar terrains, we have studied Reactive Oxygen Species (ROS) generation by a suite of lunar simulants of different mineralogical-chemical composition dispersed in water and Simulated Lung Fluid (SLF). To further explore the reactivity of simulants under lunar environmental conditions, we compared the reactivity of simulants both in air and inert atmosphere. As the impact of micrometeorites with consequent shock-induced stresses is a major environmental factor on the Moon, we also studied the effect of mechanical stress on samples. Mechanical stress was induced by hand crushing the samples both in air and inert atmosphere. The reactivity of samples after crushing was analyzed for a period of up to nine days. Hydrogen peroxide (H2O2) in water and SLF was analyzed by an in situ electrochemical probe and hydroxyl radical (•OH) by Electron Spin Resonance (ESR) spectroscopy and Adenine probe. Out of all simulants, CSM-CL-S was found to be the most reactive simulant followed by OB-1 and then JSC-1A simulant. The overall reactivity of samples in the inert atmosphere was higher than in air. Fresh crushed samples showed a higher level of reactivity than uncrushed samples. Simulant samples treated to create agglutination, including the formation of zero-valent iron, showed less reactivity than untreated simulants. ROS generation in SLF is initially slower than in deionized water (DI), but the ROS formation is sustained for as long as 7.5 h. By contrast ROS is formed rapidly within 30 min when simulants are dispersed in DI, but then the concentration either stabilizes or decreases over time. The results indicate that mechanical stress and the absence of molecular oxygen and water, which are important environmental characteristics of the lunar environment, can lead to enhanced production of ROS in general. However, compositional difference among simulants is the most important factor in governing the production of ROS. Simulants with glass content in excess of 40 wt% appear to produce as much as of order of magnitude more ROS than simulants with lower glass content.

  2. A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

    PubMed

    DeLeon, Eric R; Gao, Yan; Huang, Evelyn; Arif, Maaz; Arora, Nitin; Divietro, Alexander; Patel, Shivali; Olson, Kenneth R

    2016-04-01

    Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter. Here, we compared ROS to RSS sensitivity of five common ROS methods: redox-sensitive green fluorescent protein (roGFP), 2', 7'-dihydrodichlorofluorescein, MitoSox Red, Amplex Red, and amperometric electrodes. All methods detected RSS and were as, or more, sensitive to RSS than to ROS. roGFP, arguably the "gold standard" for ROS measurement, was more than 200-fold more sensitive to the mixed polysulfide H2Sn(n= 1-8) than to H2O2 These findings suggest that RSS may be far more prevalent in intracellular signaling than previously appreciated and that the contribution of ROS may be overestimated. This conclusion is further supported by the observation that estimated daily sulfur metabolism and ROS production are approximately equal and the fact that both RSS and antioxidant mechanisms have been present since the origin of life, nearly 4 billion years ago, long before the rise in environmental oxygen 600 million years ago. Although ROS are assumed to be the most biologically relevant oxidants, our results question this paradigm. We also anticipate our findings will direct attention toward development of novel and clinically relevant anti-(RSS)-oxidants. PMID:26764057

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

    PubMed Central

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

    2013-01-01

    Degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. The two-step oxidation of proline is catalyzed by proline oxidase and Δ1-pyrroline-5-carboxylate (P5C) dehydrogenase, which produce P5C and glutamate, respectively. In animal and plant cells, impairment of P5C dehydrogenase activity results in P5C-proline cycling when exogenous proline is supplied via the actions of proline oxidase and P5C reductase (the enzyme that converts P5C to proline). This proline is oxidized by the proline oxidase-FAD complex that delivers electrons to the electron transport chain and to O2, leading to mitochondrial reactive oxygen species (ROS) overproduction. Coupled activity of proline oxidase and P5C dehydrogenase is therefore important for maintaining ROS homeostasis. In the genome of the fungal pathogen Cryptococcus neoformans, there are two paralogs (PUT1 and PUT5) that encode proline oxidases and a single ortholog (PUT2) that encodes P5C dehydrogenase. Transcription of all three catabolic genes is inducible by the presence of proline. However, through the creation of deletion mutants, only Put5 and Put2 were found to be required for proline utilization. The put2Δ mutant also generates excessive mitochondrial superoxide when exposed to proline. Intracellular accumulation of ROS is a critical feature of cell death; consistent with this fact, the put2Δ mutant exhibits a slight, general growth defect. Furthermore, Put2 is required for optimal production of the major cryptococcal virulence factors. During murine infection, the put2Δ mutant was discovered to be avirulent; this is the first report highlighting the importance of P5C dehydrogenase in enabling pathogenesis of a microorganism. PMID:23564202

  4. Reactive Oxygen Species Alter Autocrine and Paracrine Signaling

    SciTech Connect

    Zangar, Richard C.; Bollinger, Nikki; Weber, Thomas J.; Tan, Ruimin; Markillie, Lye Meng; Karin, Norman J.

    2011-12-01

    Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endo-plasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A customELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-{kappa}B pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.

  5. Role of Reactive Oxygen Species-Mediated Signaling in Aging

    PubMed Central

    Labunskyy, Vyacheslav M.

    2013-01-01

    Abstract Significance: Redox biology is a rapidly developing area of research due to the recent evidence for general importance of redox control for numerous cellular functions under both physiological and pathophysiological conditions. Understanding of redox homeostasis is particularly relevant to the understanding of the aging process. The link between reactive oxygen species (ROS) and accumulation of age-associated oxidative damage to macromolecules is well established, but remains controversial and applies only to a subset of experimental models. In addition, recent studies show that ROS may function as signaling molecules and that dysregulation of this process may also be linked to aging. Recent Advances: Many protein factors and pathways that control ROS production and scavenging, as well as those that regulate cellular redox homeostasis, have been identified. However, much less is known about the mechanisms by which redox signaling pathways influence longevity. In this review, we discuss recent advances in the understanding of the molecular basis for the role of redox signaling in aging. Critical Issues: Recent studies allowed identification of previously uncharacterized redox components and revealed complexity of redox signaling pathways. It would be important to identify functions of these components and elucidate how distinct redox pathways are integrated with each other to maintain homeostatic balance. Future Directions: Further characterization of processes that coordinate redox signaling, redox homeostasis, and stress response pathways should allow researchers to dissect how their dysregulation contributes to aging and pathogenesis of various age-related diseases, such as diabetes, cancer and neurodegeneration. Antioxid. Redox Signal. 19, 1362–1372. PMID:22901002

  6. Respiration in adipocytes is inhibited by reactive oxygen species.

    PubMed

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

    2010-08-01

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

  7. Reactive Oxygen Species Regulate Nucleostemin Oligomerization and Protein Degradation*

    PubMed Central

    Huang, Min; Whang, Patrick; Chodaparambil, Jayanth V.; Pollyea, Daniel A.; Kusler, Brenda; Xu, Liwen; Felsher, Dean W.; Mitchell, Beverly S.

    2011-01-01

    Nucleostemin (NS) is a nucleolar-nucleoplasmic shuttle protein that regulates cell proliferation, binds p53 and Mdm2, and is highly expressed in tumor cells. We have identified NS as a target of oxidative regulation in transformed hematopoietic cells. NS oligomerization occurs in HL-60 leukemic cells and Raji B lymphoblasts that express high levels of c-Myc and have high intrinsic levels of reactive oxygen species (ROS); reducing agents dissociate NS into monomers and dimers. Exposure of U2OS osteosarcoma cells with low levels of intrinsic ROS to hydrogen peroxide (H2O2) induces thiol-reversible disulfide bond-mediated oligomerization of NS. Increased exposure to H2O2 impairs NS degradation, immobilizes the protein within the nucleolus, and results in detergent-insoluble NS. The regulation of NS by ROS was validated in a murine lymphoma tumor model in which c-Myc is overexpressed and in CD34+ cells from patients with chronic myelogenous leukemia in blast crisis. In both instances, increased ROS levels were associated with markedly increased expression of NS protein and thiol-reversible oligomerization. Site-directed mutagenesis of critical cysteine-containing regions of nucleostemin altered both its intracellular localization and its stability. MG132, a potent proteasome inhibitor and activator of ROS, markedly decreased degradation and increased nucleolar retention of NS mutants, whereas N-acetyl-l-cysteine largely prevented the effects of MG132. These results indicate that NS is a highly redox-sensitive protein. Increased intracellular ROS levels, such as those that result from oncogenic transformation in hematopoietic malignancies, regulate the ability of NS to oligomerize, prevent its degradation, and may alter its ability to regulate cell proliferation. PMID:21242306

  8. Are mitochondrial reactive oxygen species required for autophagy?

    SciTech Connect

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

    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.

  9. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  10. The interaction of atmospheric pressure plasma jets with cancer and normal cells: generation of intracellular reactive oxygen species and changes of the cell proliferation and cell cycle

    NASA Astrophysics Data System (ADS)

    Chung, Tae Hun; Joh, Hea Min; Kim, Sun Ja; Leem, Sun Hee

    2013-09-01

    The possibility of atmospheric pressure plasmas is emerging as a candidate in cancer therapy. The primary role is played by reactive oxygen species (ROS), UV photons, charged particles and electric fields. Among them, intracellular ROS induced by plasma are considered to be the key constituents that induce cellular changes and apoptosis. In this study, the effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. The plasma treatment was performed under different working gases, applied voltages, gas flow rates, and with and without additive oxygen flow. Using a detection dye, we observed that plasma exposure leads to the increase of the intracellular ROS and that the intracellular ROS production can be controlled by plasma parameters. A significant ROS generation was induced by plasma exposure on cancer cells and the overproduction of ROS contributes to the reduced cell proliferation. Normal cells were observed to be less affected by the plasma-mediated ROS and cell proliferation was less changed. The plasma treatment also resulted in the alteration of the cell cycle that contributes to the induction of apoptosis in cancer cells. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as cancer therapy. This work was supported by the National Research Foundation of Korea under Contract No. 2012R1A1A2002591 and 2012R1A1A3010213.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

    Abstract Significance: Extensive research during the last quarter century has revealed that reactive oxygen species (ROS) produced in the body, primarily by the mitochondria, play a major role in various cell-signaling pathways. Most risk factors associated with chronic diseases (e.g., cancer), such as stress, tobacco, environmental pollutants, radiation, viral infection, diet, and bacterial infection, interact with cells through the generation of ROS. Recent Advances: ROS, in turn, activate various transcription factors (e.g., nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB], activator protein-1, hypoxia-inducible factor-1α, and signal transducer and activator of transcription 3), resulting in the expression of proteins that control inflammation, cellular transformation, tumor cell survival, tumor cell proliferation and invasion, angiogenesis, and metastasis. Paradoxically, ROS also control the expression of various tumor suppressor genes (p53, Rb, and PTEN). Similarly, γ-radiation and various chemotherapeutic agents used to treat cancer mediate their effects through the production of ROS. Interestingly, ROS have also been implicated in the chemopreventive and anti-tumor action of nutraceuticals derived from fruits, vegetables, spices, and other natural products used in traditional medicine. Critical Issues: These statements suggest both “upside” (cancer-suppressing) and “downside” (cancer-promoting) actions of the ROS. Thus, similar to tumor necrosis factor-α, inflammation, and NF-κB, ROS act as a double-edged sword. This paradox provides a great challenge for researchers whose aim is to exploit ROS stress for the development of cancer therapies. Future Directions: The various mechanisms by which ROS mediate paradoxical effects are discussed in this article. The outstanding questions and future directions raised by our current understanding are discussed. Antioxid. Redox Signal. 16, 1295–1322. PMID:22117137

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

    SciTech Connect

    Liu Qibing; Liu Lulu; Lu Yingmei; Tao Rongrong; Huang Jiyun; Shioda, Norifumi; Moriguchi, Shigeki; Fukunaga, Kohji; Han Feng; Lou Yijia

    2010-05-01

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

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

    PubMed

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

    2012-07-01

    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. PMID:22706644

  15. Chemically active species in an Oxygen Inductively Coupled Plasma

    NASA Astrophysics Data System (ADS)

    Ly, Nathaniel; Boffard, John; Lin, Chun; Wendt, Amy; Radovanov, Svetlana; Persing, Harold; Likhanskii, Alexandre

    2015-09-01

    Oxygen plasmas are used in a wide variety of applications including ion implantation and photoresist striping. Here we combine noninvasive optical emission spectroscopy (OES) measurements and numerical simulations to investigate the plasma parameters in both oxygen inductively coupled plasmas (ICP) and oxygen-argon ICPs. An emission model makes use of available electron impact excitation cross sections for atomic and molecular oxygen to relate measured O and O2+emission intensities to corresponding plasma parameters, including the electron temperature, electron density, and the dissociation fraction of the neutral oxygen. For plasma simulations we use the CRTRS, 2D/3D code that selfconsistently solves for ICP power deposition, electrostatic potential and plasma dynamics in the driftdiffusion approximation (or full momentum equations). Comparison of the experimental OES measurements are used to check the validity of the plasma simulation which yields results that the OES approach has difficulty in measuring including the relative fluxes of O+ and O2+,which is important for ion implantation. The authors acknowledge support from NSF Grant PHY-1068670, and from Dr. Shahid Rauf for developing CRTRS.

  16. Frequency effects on the production of reactive oxygen species in atmospheric radio frequency helium-oxygen discharges

    SciTech Connect

    Zhang, Yuantao T.; He Jin

    2013-01-15

    Several experimental and computational studies have shown that increasing frequency can effectively enhance the discharge stability in atmospheric radio-frequency (rf) discharges, but the frequency effects on the reactivity of rf discharges, represented by the densities of reactive oxygen species (ROS), are still far from fully understood. In this paper, a one-dimensional fluid model with 17 species and 65 reactions taken into account is used to explore the influences of the driving frequency on the production and destruction of ROS in atmospheric rf helium-oxygen discharges. From the computational results, with an increase in the frequency the densities of ROS decrease always at a constant power density, however, in the relatively higher frequency discharges the densities of ROS can be effectively improved by increasing the input power density with an expanded oxygen admixture range, while the discharges operate in the {alpha} mode, and the numerical data also show the optimal oxygen admixture for ground state atomic oxygen, at which the peak atomic oxygen density can be obtained, increases with the driving frequency.

  17. Quantitative assessment of reactive oxygen species generation by cavitation incepted efficiently using nonlinear propagation effect

    NASA Astrophysics Data System (ADS)

    Yasuda, Jun; Yoshizawa, Shin; Umemura, Shin-ichiro

    2015-10-01

    Sonodynamic treatment is a treatment method that uses chemical bio-effect of cavitation bubbles. Reactive oxygen species that can kill cancerous tissue is induced by such chemical effect of cavitation bubbles and it is important to generate them efficiently for effective sonodynamic treatment. Cavitation cloud can be formed by an effect of nonlinear propagation and focus and in this study, it was experimentally investigated if cavitation cloud was useful for efficient generation of reactive oxygen species. As a result, it was demonstrated that cavitation cloud would be useful for efficient generation of reactive oxygen species.

  18. Overproduction timing errors in expert dancers.

    PubMed

    Minvielle-Moncla, Joëlle; Audiffren, Michel; Macar, Françoise; Vallet, Cécile

    2008-07-01

    The authors investigated how expert dancers achieve accurate timing under various conditions. They designed the conditions to interfere with the dancers' attention to time and to test the explanation of the interference effect provided in the attentional model of time processing. Participants were 17 expert contemporary dancers who performed a freely chosen duration while walking and executing a bilateral cyclic arm movement over a given distance. The dancers reproduced that duration in different situations of interference. The process yielded temporal overproductions, validating the attentional model and extending its application to expert populations engaged in complex motor situations. The finding that the greatest overproduction occurred in the transfer-with-improvisation condition suggests that improvisation within a time deadline requires specific training. PMID:18628106

  19. Cytotoxic and Antitumor Activity of Sulforaphane: The Role of Reactive Oxygen Species

    PubMed Central

    Sestili, Piero; Fimognari, Carmela

    2015-01-01

    According to recent estimates, cancer continues to remain the second leading cause of death and is becoming the leading one in old age. Failure and high systemic toxicity of conventional cancer therapies have accelerated the identification and development of innovative preventive as well as therapeutic strategies to contrast cancer-associated morbidity and mortality. In recent years, increasing body of in vitro and in vivo studies has underscored the cancer preventive and therapeutic efficacy of the isothiocyanate sulforaphane. In this review article, we highlight that sulforaphane cytotoxicity derives from complex, concurring, and multiple mechanisms, among which the generation of reactive oxygen species has been identified as playing a central role in promoting apoptosis and autophagy of target cells. We also discuss the site and the mechanism of reactive oxygen species' formation by sulforaphane, the toxicological relevance of sulforaphane-formed reactive oxygen species, and the death pathways triggered by sulforaphane-derived reactive oxygen species. PMID:26185755

  20. COMPARATIVE ANALYSIS OF REACTIVE OXYGEN SPECIES IN HUMAN PLASMA AND BLOOD

    EPA Science Inventory

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

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

    EPA Science Inventory

    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...

  2. Species-Level Variability in Extracellular Production Rates of Reactive Oxygen Species by Diatoms

    PubMed Central

    Schneider, Robin J.; Roe, Kelly L.; Hansel, Colleen M.; Voelker, Bettina M.

    2016-01-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O2-) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O2- were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O2- and H2O2 was examined by measuring recovery of O2- and H2O2 added to the influent medium. O2- production rates ranged from undetectable to 7.3 × 10−16 mol cell−1 h−1, while H2O2 production rates ranged from undetectable to 3.4 × 10−16 mol cell−1 h−1. Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O2- in light than dark, even when the organisms were killed, indicating that O2- is produced via a passive photochemical process on the cell surface. The ratio of H2O2 to O2- production rates was consistent with production of H2O2 solely through dismutation of O2- for T. oceanica, while T. pseudonana made much more H2O2 than O2-. T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94–100% H2O2; 10–80% O2-) were consistently higher than those for live cultures (65–95% H2O2; 10–50% O2-). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O2- decay appeared to occur via a combination of active and passive processes. Overall, this study shows that the rates and pathways for ROS production and decay vary greatly among diatom species, even between those that are closely related, and as a function of light conditions. PMID:27066475

  3. UV-B-induced formation of reactive oxygen species and oxidative damage of the cyanobacterium Anabaena sp.: protective effects of ascorbic acid and N-acetyl-L-cysteine.

    PubMed

    He, Yu-Ying; Hder, Donat P

    2002-03-01

    Reactive oxygen species (ROS) are involved in the oxidative damage of the cyanobacterium Anabaena sp. caused by UV-B (280-315 nm) radiation. UV-B-induced overproduction of ROS as well as the oxidative stress was detected in vivo by using the ROS-sensitive probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Thiobarbituric acid reactive substances (TBARS) and fluorometric analysis of DNA unwinding (FADU) methods were adapted to measure lipid peroxidation and DNA strand breaks in Anabaena sp. Moderate UV-B radiation causes an increase of ROS production, enhanced lipid peroxidation and DNA strand breaks, yielding a significantly decreased survival. In contrast, the supplementation of UV-A in our work only showed a significant increase in total ROS levels and DNA strand breaks while no significant effect on lipid peroxidation, chlorophyll bleaching or survival was observed. The presence of ascorbic acid and N-acetyl-L-cysteine (NAC) reversed the oxidative stress and protected the organisms from chlorophyll bleaching and the damage of photosynthetic apparatus induced by UV-B significantly, resulting in a considerably higher survival rate. Ascorbic acid also exhibited a significant protective effect on lipid peroxidation and DNA strand breaks while NAC did not show a substantial effect. These results suggest that ascorbic acid exhibited significantly higher protective efficiency with respect to DNA strand breaks and survival than NAC while NAC appears to be especially effective in defending the photosynthetic apparatus from oxidative damage. PMID:11897511

  4. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. PMID:24518820

  5. N-Acetyl Cysteine Depletes Reactive Oxygen Species and Prevents Dental Monomer-Induced Intrinsic Mitochondrial Apoptosis In Vitro in Human Dental Pulp Cells

    PubMed Central

    Li, Jing; Shan, Lequn; Liu, Qian; Liu, Ying; Song, Qian; Yu, Fan; Yu, Haohan; Liu, Huan; Huang, Li; Chen, Jihua

    2016-01-01

    Purpose To investigate the involvement of intrinsic mitochondrial apoptosis in dental monomer-induced cytotoxicity and the influences of N-acetyl cysteine (NAC) on this process. Methods Human dental pulp cells (hDPCs) were exposed to several dental monomers in the absence or presence of NAC, and cell viability, intracellular redox balance, morphology and function of mitochondria and key indicators of intrinsic mitochondrial apoptosis were evaluated using various commercial kits. Results Dental monomers exerted dose-dependent cytotoxic effects on hDPCs. Concomitant to the over-production of reactive oxygen species (ROS) and depletion of glutathione (GSH), differential changes in activities of superoxide dismutase, glutathione peroxidase, and catalase were detected. Apoptosis, as indicated by positive Annexin V/propidium iodide (PI) staining and activation of caspase-3, was observed after dental monomer treatment. Dental monomers impaired the morphology and function of mitochondria, and induced intrinsic mitochondrial apoptosis in hDPCs via up-regulation of p53, Bax and cleaved caspase-3, and down-regulation of Bcl-2. NAC restored cell viability, relieved oxidative stress and blocked the apoptotic effects of dental monomers. Conclusions Dental monomers induced oxidative stress and mitochondrial intrinsic apoptosis in hDPCs. NAC could reduce the oxidative stress and thus protect hDPCs against dental monomer-induced apoptosis. PMID:26808507

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

    SciTech Connect

    Nicolescu, Adrian C. Ji, Yanbin; Comeau, Jeannette L.; Hill, Bruce C.; Takahashi, Takashi; Brien, James F.; Racz, William J.; Massey, Thomas E.

    2008-03-15

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

  7. Metabolic regulation and overproduction of primary metabolites

    PubMed Central

    Sanchez, Sergio; Demain, Arnold L.

    2008-01-01

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

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

    SciTech Connect

    Park, Hae-Ryung Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-15

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

  9. Early joint degeneration and antagonism between growth factors and reactive oxygen species. Is non-surgical management possible?

    PubMed Central

    MANUNTA, ANDREA FABIO; ZEDDE, PIETRO; CUDONI, SEBASTIANO; CAGGIARI, GIANFILIPPO; PINTUS, GIANFRANCO

    2015-01-01

    Purpose in pathological conditions such as osteo-arthritis (OA), overproduction of reactive oxygen species (ROS) may overwhelm the antioxidant defenses of chondrocytes, thus promoting oxidative stress and cell death. It can be hypothesized that increasing the antioxidant machinery of chondrocytes may prevent the age-associated progression of this disease. Growth factors (GFs) play an important role in promoting both the resolution of inflammatory processes and tissue repair. In view of these considerations, we set out to investigate the protective effect, against H2O2-induced oxidative cell death, potentially exerted by fluid drained from the joint postoperatively. Methods the present study was conducted in 20 patients diagnosed with bilateral knee osteoarthritis and treated, between January 2013 and June 2014, with prosthetic knee implantation on the side more affected by the arthritic process, together with intraoperative placement of a closed-circuit drainage aspiration system. As a result, 20 different serum samples were collected from the drained articular fluid, prepared using two different methodologies. In addition, forty blood serum samples were obtained and prepared: 20 from the surgically treated patients and 20 from healthy controls. The present work was undertaken to investigate the potential protective effect of sera obtained from articular fluid drainage against hydrogen peroxide-induced oxidative stress in cultured human chondrocytes. Results exposure of chondrocytes to hydrogen peroxide elicited a dose-dependent increase in oxidative stress and chondrocyte cell death, phenomena that were significantly counteracted by the pre-treatment of cell cultures with sera from articular fluid drainage. Conclusions oxidatively stressed chondrocytes treated with sera obtained from articular fluid drainage lived longer than those treated with blood serum samples and longer than untreated ones. Clinical Relevance synovial fluids are usually discarded once the drainage reservoir is full; instead they could benefit the patients from whom they are collected, as they are rich in growth factors and they may act as antagonists of ROS effects. Accordingly, they could be used to treat chondropathies, early OA, and mild OA located in other sites. PMID:26889468

  10. Roles of Reactive Oxygen and Nitrogen Species in Pain

    PubMed Central

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

    2011-01-01

    Peroxynitrite (PN, ONOO−) and its reactive oxygen precursor superoxide (SO, O2·−), are critically important in the development of pain of several etiologies including in the development of pain associated with chronic use of opiates such as morphine (also known as opiate-induced hyperalgesia and antinociceptive tolerance). This is now an emerging field in which considerable progress has been made in terms of understanding the relative contribution of SO, PN, and nitroxidative stress in pain signaling at the molecular and biochemical levels. Aggressive research in this area is poised to provide the pharmacological basis for development of novel non-narcotic analgesics that are based upon the unique ability to selectively eliminate SO and/or PN. As we have a better understanding of the role of SO and PN in pathophysiological settings, targeting PN may be a better therapeutic strategy than targeting SO. This is due to the fact that unlike PN, which has no currently known beneficial role, SO may play a significant role in learning and memory [1]. Thus, the best approach may be to spare SO while directly targeting its downstream product, PN. Over the last 15 years, our team has spearheaded research concerning the roles of SO/PN in pain and these results are currently leading to the development of solid therapeutic strategies in this important area. PMID:21277369

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

    NASA Technical Reports Server (NTRS)

    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.

  12. Proline does not quench singlet oxygen: evidence to reconsider its protective role in plants.

    PubMed

    Signorelli, Santiago; Arellano, Juan Bautista; Melø, Thor Bernt; Borsani, Omar; Monza, Jorge

    2013-03-01

    Plants are commonly subjected to several environmental stresses that lead to an overproduction of reactive oxygen species (ROS). As plants accumulate proline in response to stress conditions, some authors have proposed that proline could act as a non-enzymatic antioxidant against ROS. One type of ROS aimed to be quenched by proline is singlet oxygen ((1)O(2))-molecular oxygen in its lowest energy electronically excited state-constitutively generated in oxygenic, photosynthetic organisms. In this study we clearly prove that proline cannot quench (1)O(2) in aqueous buffer, giving rise to a rethinking about the antioxidant role of proline against (1)O(2). PMID:23384940

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation.

    PubMed

    Tahara, Erich B; Navarete, Felipe D T; Kowaltowski, Alicia J

    2009-05-01

    Reactive oxygen species are a by-product of mitochondrial oxidative phosphorylation, derived from a small quantity of superoxide radicals generated during electron transport. We conducted a comprehensive and quantitative study of oxygen consumption, inner membrane potentials, and H(2)O(2) release in mitochondria isolated from rat brain, heart, kidney, liver, and skeletal muscle, using various respiratory substrates (alpha-ketoglutarate, glutamate, succinate, glycerol phosphate, and palmitoyl carnitine). The locations and properties of reactive oxygen species formation were determined using oxidative phosphorylation and the respiratory chain modulators oligomycin, rotenone, myxothiazol, and antimycin A and the uncoupler CCCP. We found that in mitochondria isolated from most tissues incubated under physiologically relevant conditions, reactive oxygen release accounts for 0.1-0.2% of O(2) consumed. Our findings support an important participation of flavoenzymes and complex III and a substantial role for reverse electron transport to complex I as reactive oxygen species sources. Our results also indicate that succinate is an important substrate for isolated mitochondrial reactive oxygen production in brain, heart, kidney, and skeletal muscle, whereas fatty acids generate significant quantities of oxidants in kidney and liver. Finally, we found that increasing respiratory rates is an effective way to prevent mitochondrial oxidant release under many, but not all, conditions. Altogether, our data uncover and quantify many tissue-, substrate-, and site-specific characteristics of mitochondrial ROS release. PMID:19245829

  15. Inactivation of Pathogenic Bacteria on Seeds by Active Oxygen Species Generated in Low-Pressure Plasma

    NASA Astrophysics Data System (ADS)

    Ono, Reoto; Uchida, Shohei; Hayashi, Nobuya; Kosaka, Rina; Soeda, Yasutaka

    2015-09-01

    The inactivation of bacteria on seeds by active oxygen species generated by a low-pressure oxygen plasma is investigated. Species of active oxygen contributing to the inactivation of bacteria are attempted to be identified. Cylindrical stainless chamber with the internal volume of 17 L is used and RF antenna is set inside the chamber. The oxygen gas pressure is 20-100 Pa. RF power of 13.56 MHz is supplied to RF antenna and CCP is generated. After irradiation, bacteria are extracted from seeds and cultivated on nutrient agars. The number of colonies on these agars is counted after 48 h incubation. The number of bacteria on seeds decreases to less than 10-3 after plasma irradiation for 45 min comparing with that of control. The tendency of the reduction rate of bacteria on seeds has positive correlation with that of the light emission intensity of the singlet excited oxygen molecule as the oxygen gas pressure is varied. It is supposed that the singlet excited oxygen molecule would be one of the major factors for the inactivation of bacteria on seeds.

  16. Molecular mechanisms for the reaction between (˙)OH radicals and proline: insights on the role as reactive oxygen species scavenger in plant stress.

    PubMed

    Signorelli, Santiago; Coitiño, E Laura; Borsani, Omar; Monza, Jorge

    2014-01-01

    The accumulation of proline (Pro) and overproduction of reactive oxygen species (ROS) by plants exposed to stress is well-documented. In vitro assays show that enzyme inactivation by hydroxyl radicals ((•)OH) can be avoided in the presence of Pro, suggesting this amino acid might act as a (•)OH scavenger. Although production of hydroxyproline (Hyp) has been hypothesized in connection with such antioxidant activity, no evidence on the detailed mechanism of scavenging has been reported. To elucidate whether and how Hyp might be produced, we used density functional theory calculations coupled to a polarizable continuum model to explore 27 reaction channels including H-abstraction by (•)OH and (•)OH/H2O addition. The structure and energetics of stable species and transition states for each reaction channel were characterized at the PCM-(U)M06/6-31G(d,p) level in aqueous solution. Evidence is found for a main pathway in which Pro scavenges (•)OH by successive H-abstractions (ΔG(‡,298) = 4.1 and 7.5 kcal mol(-1)) to yield 3,4-Δ-Pro. A companion pathway with low barriers yielding Δ(1)-pyrroline-5-carboxylate (P5C) is also supported, linking with 5-Hyp through hydration. However, this connection remains unlikely in stressed plants because P5C would be efficiently recycled to Pro (contributing to its accumulation) by P5C reductase, hypothesis coined here as the "Pro-Pro cycle". PMID:24328335

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  19. Fusogenic Reactive Oxygen Species Triggered Charge-Reversal Vector for Effective Gene Delivery.

    PubMed

    Liu, Xin; Xiang, Jiajia; Zhu, Dingcheng; Jiang, Liming; Zhou, Zhuxian; Tang, Jianbin; Liu, Xiangrui; Huang, Yongzhuo; Shen, Youqing

    2016-03-01

    A novel fusogenic lipidic polyplex (FLPP) vector is designed to fuse with cell membranes, mimicking viropexis, and eject the polyplex into the cytosol, where the cationic polymer is subsequently oxidized by intracellular reactive oxygen species and converts to being negatively charged, efficiently releasing the DNA. The vector delivering suicide gene achieves significantly better inhibition of tumor growth than doxorubicin. PMID:26663349

  20. NADPH Oxidase- and Mitochondria-derived Reactive Oxygen Species in Proinflammatory Microglial Activation: A Bipartisan Affair?

    PubMed Central

    Bordt, Evan A.; Polster, Brian M.

    2014-01-01

    Microglia are the resident immune cells of the brain and play major roles in central nervous system development, maintenance, and disease. Brain insults cause microglia to proliferate, migrate, and transform into one or more activated states. Classical M1 activation triggers the production of proinflammatory factors such as tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO), and reactive oxygen species which, in excess, can exacerbate brain injury. The mechanisms underlying microglial activation are not fully understood, yet reactive oxygen species are increasingly implicated as mediators of microglial activation. In this review, we highlight studies linking reactive oxygen species, in particular hydrogen peroxide derived from NADPH oxidase-generated superoxide, to the classical activation of microglia. In addition, we critically evaluate controversial evidence suggesting a specific role for mitochondrial reactive oxygen species in the activation of the NLRP3 inflammasome, a multiprotein complex that mediates the production of IL-1β and IL-18. Finally, the limitations of common techniques used to implicate mitochondrial ROS in microglial and inflammasome activation, such as the use of the mitochondrially-targeted ROS indicator MitoSOX and the mitochondrially-targeted antioxidant MitoTEMPO, are also discussed. PMID:25091898

  1. Reactive Oxygen Species Are Involved in Plant Defense against a Gall Midge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) play a major role in plant defense against pathogens, but evidence for their role in defense against insects is still preliminary and inconsistent. In this study, we examined the potential role of ROS in defense of wheat and rice against Hessian fly (Mayetiola destruct...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Mitochondrial function and reactive oxygen species action in relation to boar motility.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric assays of viable boar sperm were developed to measure reactive oxygen species (ROS) formation (oxidization of hydroethidine to ethidium), membrane lipid peroxidation (oxidation of lipophilic probe C11-BODIPY581/591), and mitochondrial inner transmembrane potential (aggregation of mit...

  4. Mitochondrial function and reactive oxygen species action in relation to boar motility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric assays were developed for reactive oxygen species (ROS) formation (ROS-induced oxidization of hydroethidine to ethidium), membrane lipid peroxidation (C11-BODIPY-581/591 oxidation), and mitochondrial transmembrane potential (MMP) (MMP-induced JC-1 aggregation, red fluorescence) in vi...

  5. Effects of reactive oxygen species action on sperm function in spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) formation and lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic because of the low specificity and sens...

  6. Water-soluble fullerene materials for bioapplications: photoinduced reactive oxygen species generation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The photoinduced reactive oxygen species (ROS) generation from several water-soluble fullerenes was examined. Macromolecular or small molecular water-soluble fullerene complexes/derivatives were prepared and their 1O2 and O2•- generation abilities were evaluated by EPR spin-trapping methods. As a r...

  7. Hyperoxia, reactive oxygen species, and hyperventilation: oxygen sensitivity of brain stem neurons.

    PubMed

    Dean, Jay B; Mulkey, Daniel K; Henderson, Richard A; Potter, Stephanie J; Putnam, Robert W

    2004-02-01

    Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2 receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2 and reactive O2 species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2 and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2 has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2 and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed. PMID:14715688

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

    PubMed

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

    2013-07-01

    Data on low dissolved oxygen (DO₂) tolerance of freshwater fish species of north-western Europe were used to create species sensitivity distributions (SSD). Lowest observed effect concentrations (LOEC) and 100% lethal concentrations (LC₁₀₀) data were collected from the scientific literature. Comparisons were made among life stages as well as between native and exotic species. In addition, lethal DO₂ concentrations were compared to oxygen concentrations corresponding to maximum tolerable water temperatures of the same species. Fish eggs and embryos were the least tolerant. Juveniles had a significantly lower mean LOEC than adults, but there was no difference in mean LC₁₀₀ between the two groups. The difference in lethal oxygen concentrations between adults and juveniles was largest for three salmonids, although it remains uncertain if this was a result of smoltification. There were no significant differences between native and exotic species; however, data on exotics are limited. DO₂ concentrations converted from maximum tolerable water temperatures were 3·9 times higher than the measured lethal DO₂ concentrations, which may reflect changes in respiration rates (Q₁₀) and may also relate to the simplicity of the model used. PMID:23808700

  9. The interdependence of the reactive species of oxygen, nitrogen, and carbon.

    PubMed

    Bild, Walther; Ciobica, Alin; Padurariu, Manuela; Bild, Veronica

    2013-03-01

    This mini-review tries to summarize the main interdependences between the free radicals of oxygen, nitrogen, and carbon. Also, the main metabolic pathways for these radical species are described, as well as how these affect their interaction and functional implications. Emphasis is made on the metabolic disturbances induced by stressing aggressions that produce radical species. In this way, cellular oxidative imbalances created by the superiority of reactive oxygen species over the antioxidant systems produce both activation of nitroxide synthases and the oxidation of terminal nitrogen from L-arginine, as well as the metabolization of heme until carbon monoxide by nitric oxide-activated hemoxygenase. Also, multiple cellular protein and nucleoprotein alterations determined by these three kinds of radical species are completed by the involvement of hydrogen sulfide, which results from the degradation of L-cysteine by cistationine-γ-lyase. In this way, sufficient experimental data tend to demonstrate the involvement of hydrogen sulfide and other thiol derivatives in the interrelations between oxygen, nitrogen, and carbon, which results in a true radical cascade. Thus, oxidative stress, together with nitrosative and carbonilic stress, may constitute a central point where other factors of vulnerability meet, and their interactions could have an important impact in many modern diseases. Considering that the actions of reactive species can be most of the time corrected, future studies need to establish the therapeutical importance of various agents which modulate oxidative, nitrosative, or carbonilic stress. PMID:22456998

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

    PubMed Central

    Asghar, Waseem; Velasco, Vanessa; Kingsley, James L.; Shoukat, Muhammad S.; Shafiee, Hadi; Anchan, Raymond M.; Mutter, George L.; Tüzel, Erkan; Demirci, Utkan

    2014-01-01

    Fertilization and reproduction are central to the survival and propagation of a species. Couples who cannot reproduce naturally have to undergo in vitro clinical procedures. An integral part of these clinical procedures includes isolation of healthy sperm from raw semen. Existing sperm sorting methods are not efficient and isolate sperm having high DNA fragmentation and reactive oxygen species, and suffer from multiple manual steps and variations between embryologists. Inspired by in vivo natural sperm sorting mechanisms where vaginal mucus becomes less viscous to form microchannels to guide sperm towards egg, we present a chip that efficiently sorts healthy, motile and morphologically normal sperm without centrifugation. Higher percentage of sorted sperm show significantly lesser reactive oxygen species and DNA fragmentation than the conventional swim-up method. The presented chip is an easy-to-use high throughput sperm sorter that provides standardized sperm sorting assay with less reliance on embryologist’s skills, facilitating reliable operational steps. PMID:24753434

  11. Ion and atomic species produced in large scale oxygen plasma used for treatments sensitive materials

    NASA Astrophysics Data System (ADS)

    Spasic, Kosta; Skoro, Nikola; Puac, Nevena; Malovic, Gordana; Petrovic, Zoran Lj.

    2013-09-01

    Asymmetric CCP plasma system operating at 13.56 MHz was successfully used for treatments of textile, seeds and polymers. Central electrode (aluminium rod) was powered electrode while the cylindrical wall of the chamber was grounded electrode. We have used mass spectrometry for detections of ions and neutrals in order to get better insight in plasma chemistry involved in surface reactions on treated samples. Besides of ions, one of the important species for surface modifications is atomic oxygen. Actinometry was used as an additional diagnostic tool to determine the extent of atomic oxygen produced in plasma. Measurements were made in several different mixtures of oxygen with addition of several percent of argon. The range of pressures investigated was 150 to 450 mTorr for powers from 100 to 500 W. Measured atomic oxygen density has a steady rise with power (1019-1020 m-3) . Apart from atomic oxygen species we have detected mass spectra of positive and negative ions. Most abundant ion was O2+while the amounts of O+ and O- were smaller by the order of magnitude compared to O2+. Supported by MESTD, RS, III41011 and ON 171037.

  12. Reactive oxygen species, lipid peroxidation and enzymatic defence systems in human spermatozoa.

    PubMed

    Griveau, J F; Dumont, E; Renard, P; Callegari, J P; Le Lannou, D

    1995-01-01

    The reactive oxygen species, hydrogen peroxide (H2O2) and superoxide anion (O2o-), were generated with a xanthine-xanthine oxidase system and their effect on human sperm function was studied. The action of reactive oxygen species on selected human spermatozoa resulted in a decreased capacity for ionophore-induced acrosome reaction, a decrease in sperm motility, an increase in the concentration of lipid hydroperoxides and a loss of membrane polyunsaturated fatty acids. H2O2 was the key intermediate of the deleterious effects exerted by the xanthine and xanthine oxidase. Among these parameters, the acrosome reaction appeared most susceptible to the reactive oxygen species generated by the xanthine-xanthine oxidase system, and was decreased without sperm motility being affected. Treatment with H2O2 was shown to inactivate several enzymatic activities involved in the antioxidant defence of spermatozoa: glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase. H2O2 and O2o- were shown to be involved in the lipid alterations triggered by the xanthine-xanthine oxidase system. Singlet oxygen is proposed to intervene in the lipoperoxidation process. The inefficacy of mannitol in protecting spermatozoa suggests that hydroxyl radicals were not produced in the extracellular medium. PMID:7707295

  13. Effect of active oxygen species scavengers on fibrinolytic activity of some proteinases.

    PubMed

    Pyzhova, N S; Nikandrov, V N; Nikandrov, N N

    1996-05-15

    Scavengers of different active oxygen species affect fibrin plate lysis, catalysed by various proteinases, only at relatively high concentrations (> 10(-2) M). Singlet oxygen scavengers change proteinase activity insignificantly except for strong inhibition of pepsin and papain by sodium azide, but pepsin-by histidine, and fibrinolytic urokinase activity-by all used O2 delta 1 scavengers. Of all used scavengers of OH-radical only ethanol caused significant changes in the proteinases under study, except for alpha-chymotrypsin. The most strong inhibitory effect on proteinase activity was demonstrated by scavengers of superoxide radical. Thus, nitrotetrazolium blue strongly inhibited the activity of plasmin, urokinase (fibrinolytic activity), papain and pepsin. Catalase changed proteinase activity insignificantly, though it leads to total inhibition of pepsin activity at final 4.5 x 10(-4) M concentration. These facts and our previous findings on generating of active oxygen species by proteinases give us grounds to suppose that minor active oxygen species, endogenous for the "proteinase-substrate" system, can participate in the catalytic function of some proteinases. PMID:8743726

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

    PubMed Central

    2014-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

    Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (AL cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.

  16. Oxidases and reactive oxygen species during hematopoiesis: a focus on megakaryocytes

    PubMed Central

    Eliades, Alexia; Matsuura, Shinobu; Ravid, Katya

    2012-01-01

    Reactive oxygen species (ROS), generated as a result of various reactions, control an array of cellular processes. The role of ROS during megakaryocyte (MK) development has been a subject of interest and research. The bone marrow niche is the major site of MK differentiation and maturation. In this environment, a gradient of oxygen tension, from normoxia to hypoxia results in different levels of ROS, impacting cellular physiology. This article provides an overview of major sources of ROS, their implication in different signaling pathways, and their effect on cellular physiology, with a focus on megakaryopoiesis. The importance of ROS-generating oxidases in MK biology and pathology, including myelofibrosis, is also described. PMID:22331622

  17. Effects of membrane-bound glucose dehydrogenase overproduction on the respiratory chain of Gluconobacter oxydans.

    PubMed

    Meyer, Maria; Schweiger, Paul; Deppenmeier, Uwe

    2013-04-01

    The acetic acid bacterium Gluconobacter oxydans incompletely oxidizes carbon sources as a natural part of its metabolism, and this feature has been exploited for many biotechnological applications. The most important enzymes used to harness the biocatalytic oxidative capacity of G. oxydans are the pyrroloquinoline quinone (PQQ)-dependent dehydrogenases. The membrane-bound PQQ-dependent glucose dehydrogenase (mGDH), encoded by gox0265, was used as model protein for homologous membrane protein production using the previously described Gluconobacter expression vector pBBR1p452. The mgdh gene had ninefold higher expression in the overproduction strain compared to the parental strain. Furthermore, membranes from the overexpression strain had a five- and threefold increase of mGDH activity and oxygen consumption rates, respectively. Oxygen consumption rate of the membrane fraction could not be increased by the addition of a substrate combination of glucose and ethanol in the overproduction strain, indicating that the terminal quinol oxidases of the respiratory chain were rate limiting. In contrast, addition of glucose and ethanol to membranes of the control strain increased oxygen consumption rates approaching the observed rates with G. oxydans overproducing mGDH. The higher glucose oxidation rates of the mGDH overproduction strain corresponded to a 70 % increase of the gluconate production rate compared to the control strain. The high rate of glucose oxidation may be useful in the industrial production of gluconates and ketogluconates, or as whole-cell biosensors. Furthermore, mGDH was purified to homogeneity by one-step strep-tactin affinity chromatography and characterized. To our knowledge, this is the first report of a membrane integral quinoprotein being purified by affinity chromatography and serves as a proof-of-principle for using G. oxydans as a host for membrane protein expression and purification. PMID:22790543

  18. The Contribution of Reactive Oxygen Species to the Photobleaching of Organic Fluorophores†

    PubMed Central

    Zhou, Zhou; Blanchard, Scott C.

    2013-01-01

    Photo-excitation of fluorophores commonly used for biological imaging applications generates reactive oxygen species (ROS) which can cause bleaching of the fluorophore and damage to the biological system under investigation. In this study we show that singlet oxygen contributes relatively little to Cy5 and ATTO 647N photobleaching at low concentrations in aqueous solution. We also show that Cy5 generates significantly less ROS when covalently linked to the protective agents, cyclooctatetraene (COT), nitrobenzyl alcohol (NBA), or Trolox. Such fluorophores exhibit enhanced photostability both in bulk solutions and in single-molecule fluorescence measurements. While the fluorophores ATTO 647N and ATTO 655 showed greater photostability than Cy5 and the protective-agent linked Cy5 derivatives investigated here, both of ATTO 647N and ATTO 655 generated singlet oxygen and hydroxyl radicals at relatively rapid rates, suggesting that they may be substantially more phototoxic than Cy5 and its derivatives. PMID:24188468

  19. Electron Paramagnetic Resonance (EPR) Spectroscopy to Detect Reactive Oxygen Species in Staphylococcus aureus

    PubMed Central

    Thomas, Vinai Chittezham; Chaudhari, Sujata S.; Jones, Jocelyn; Zimmerman, Matthew C.

    2016-01-01

    Under aerobic conditions, Staphylococcus aureus (S. aureus) primarily metabolizes glucose to acetic acid. Although normally S. aureus is able to re-utilize acetate as a carbon source following glucose exhaustion, significantly high levels of acetate in the culture media may not only be growth inhibitory but also potentiates cell death in stationary phase cultures by a mechanism dependent on cytoplasmic acidification. One consequence of acetic acid toxicity is the production of reactive oxygen species (ROS). The present protocol describes the detection of ROS in S. aureus undergoing cell death by electron paramagnetic resonance (EPR) spectroscopy. Using 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) as a cell permeable spin probe, we demonstrate the detection of various oxygen radicals generated by bacteria. Although standardized for S. aureus, the methods described here should be easily adapted for other bacterial species. This protocol is adapted from Thomas et al. (2014) and Thomas et al. (2010).

  20. Biochemical changes in rat testis induced in vitro by reactive oxygen species.

    PubMed

    Nechifor, Marina Tamara; Constantin, Carolina; Manda, Gina; Neagu, Monica; Dinu, Diana

    2006-01-01

    We report the effects of reactive oxygen species generated by ultraviolet-A radiation on some biochemical parameters specific for oxidative stress, in rat testis homogenates. Results show an increase in lipid peroxidation products under ultraviolet-A exposure, and suggest that the involved mechanism is typical for a radical-mediated chain reaction. The amount of SH groups also increases during irradiation, probably as a consequence of conformational changes in proteins. Electrophoresis results revealed protein pattern changes mainly in the low molecular weight domain. The catalytic activities of alkaline phosphatase and gamma-glutamil transpeptidase are modified under the oxidative conditions generated by reactive oxygen species. The changes of the enzymatic activities are UVA exposure time-dependent, suggesting that conformational modifications are responsible for enzymatic activities enhancement. PMID:18389730

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

    PubMed Central

    Hyman, Lynne M.; Franz, Katherine J.

    2013-01-01

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

  2. Regulation of signal transduction by reactive oxygen species in the cardiovascular system

    PubMed Central

    Brown, David I.; Griendling, Kathy K.

    2015-01-01

    Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species in normal physiological signaling has been elucidated. Signaling pathways modulated by reactive oxygen species (ROS) are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here we review the current literature regarding ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. PMID:25634975

  3. Identification of different oxygen species in oxide nanostructures with (17)O solid-state NMR spectroscopy.

    PubMed

    Wang, Meng; Wu, Xin-Ping; Zheng, Sujuan; Zhao, Li; Li, Lei; Shen, Li; Gao, Yuxian; Xue, Nianhua; Guo, Xuefeng; Huang, Weixin; Gan, Zhehong; Blanc, Frédéric; Yu, Zhiwu; Ke, Xiaokang; Ding, Weiping; Gong, Xue-Qing; Grey, Clare P; Peng, Luming

    2015-02-01

    Nanostructured oxides find multiple uses in a diverse range of applications including catalysis, energy storage, and environmental management, their higher surface areas, and, in some cases, electronic properties resulting in different physical properties from their bulk counterparts. Developing structure-property relations for these materials requires a determination of surface and subsurface structure. Although microscopy plays a critical role owing to the fact that the volumes sampled by such techniques may not be representative of the whole sample, complementary characterization methods are urgently required. We develop a simple nuclear magnetic resonance (NMR) strategy to detect the first few layers of a nanomaterial, demonstrating the approach with technologically relevant ceria nanoparticles. We show that the (17)O resonances arising from the first to third surface layer oxygen ions, hydroxyl sites, and oxygen species near vacancies can be distinguished from the oxygen ions in the bulk, with higher-frequency (17)O chemical shifts being observed for the lower coordinated surface sites. H2 (17)O can be used to selectively enrich surface sites, allowing only these particular active sites to be monitored in a chemical process. (17)O NMR spectra of thermally treated nanosized ceria clearly show how different oxygen species interconvert at elevated temperature. Density functional theory calculations confirm the assignments and reveal a strong dependence of chemical shift on the nature of the surface. These results open up new strategies for characterizing nanostructured oxides and their applications. PMID:26601133

  4. Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease.

    PubMed Central

    Mossman, B T; Marsh, J P

    1989-01-01

    Asbestos is an important occupational and environmental toxicant that affects several cell types in the respiratory tract. In an effort to understand how asbestos causes cell injury and/or altered proliferation and differentiation of cells, this laboratory has focused on reactive oxygen species as mediators of asbestos-induced biological effects. A compendium of experimental results reported by this laboratory and others supports this hypothesis. For example, scavengers of reactive oxygen metabolites and iron chelators (i.e., desferroxamine) prevent cytotoxicity after addition of asbestos to a variety of cell lines and macrophages in vitro. DNA strand breakage associated with toxicity of crocidolite asbestos in C3H10T 1/2 cells also is ameliorated with use of desferroxamine. All types of asbestos cause lipid peroxidation in mammalian cells and artificial membranes, a phenomenon that can be prevented by removal of catalytic iron. Last, asbestos causes generation of active oxygen species after interaction with leukocytes or by reduction of oxygen on the surface of the fibers. Images FIGURE 1. PMID:2667992

  5. Reactive oxygen species produced upon photoexcitation of sunscreens containing titanium dioxide (an EPR study).

    PubMed

    Brezová, Vlasta; Gabcová, Sona; Dvoranová, Dana; Stasko, Andrej

    2005-05-13

    Commercial sunscreen products containing titanium dioxide were irradiated with lambda>300 nm and the formation of oxygen- (.OH, O2.-/.OOH) and carbon-centered radicals was monitored by EPR spectroscopy and spin trapping technique using 5,5-dimethyl-1-pyrroline N-oxide, alpha-phenyl-N-tert-butylnitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone as spin traps, and free nitroxide radical 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl. The photoinduced production of singlet oxygen was shown by 4-hydroxy-2,2,6,6-piperidine. The generation of reactive oxygen radical species upon irradiation of sunscreens significantly depends on their composition, as the additives present (antioxidants, radical-scavengers, solvents) can transform the reactive radicals formed to less harmful products. The continuous in situ irradiation of titanium dioxide powder, recommended for cosmetic application, investigated in different solvents (water, dimethyl sulfoxide, isopropyl myristate) resulted in the generation of oxygen-centered reactive radical species (superoxide anion radical, hydroxyl and alkoxyl radicals). PMID:15878117

  6. Identification of different oxygen species in oxide nanostructures with 17O solid-state NMR spectroscopy

    PubMed Central

    Wang, Meng; Wu, Xin-Ping; Zheng, Sujuan; Zhao, Li; Li, Lei; Shen, Li; Gao, Yuxian; Xue, Nianhua; Guo, Xuefeng; Huang, Weixin; Gan, Zhehong; Blanc, Frédéric; Yu, Zhiwu; Ke, Xiaokang; Ding, Weiping; Gong, Xue-Qing; Grey, Clare P.; Peng, Luming

    2015-01-01

    Nanostructured oxides find multiple uses in a diverse range of applications including catalysis, energy storage, and environmental management, their higher surface areas, and, in some cases, electronic properties resulting in different physical properties from their bulk counterparts. Developing structure-property relations for these materials requires a determination of surface and subsurface structure. Although microscopy plays a critical role owing to the fact that the volumes sampled by such techniques may not be representative of the whole sample, complementary characterization methods are urgently required. We develop a simple nuclear magnetic resonance (NMR) strategy to detect the first few layers of a nanomaterial, demonstrating the approach with technologically relevant ceria nanoparticles. We show that the 17O resonances arising from the first to third surface layer oxygen ions, hydroxyl sites, and oxygen species near vacancies can be distinguished from the oxygen ions in the bulk, with higher-frequency 17O chemical shifts being observed for the lower coordinated surface sites. H217O can be used to selectively enrich surface sites, allowing only these particular active sites to be monitored in a chemical process. 17O NMR spectra of thermally treated nanosized ceria clearly show how different oxygen species interconvert at elevated temperature. Density functional theory calculations confirm the assignments and reveal a strong dependence of chemical shift on the nature of the surface. These results open up new strategies for characterizing nanostructured oxides and their applications. PMID:26601133

  7. The oxygen reduction reaction (ORR) on reduced metals: evidence for a unique relationship between the coverage of adsorbed oxygen species and adsorption energy.

    PubMed

    Perry, S C; Denuault, G

    2016-04-21

    Using chronoamperometry and voltammetry at oxide-free microelectrodes in non-adsorbing electrolyte, KClO4, we investigated the reduction of oxygen containing species which adsorb at potentials below those where oxides are grown electrochemically when the electrode is exposed to dissolved oxygen. Their coverage is found to vary with the metal substrate as follows, Ni > Cu > Pt > Ag, and is negligible on Au microdiscs. This dependence is consistent with the adsorption energy of atomic oxygen for the respective metals predicted by DFT. Furthermore the adsorption energies derived from the stripping peak potentials for the different metals agree very well with those predicted by the DFT calculations. We exploit the oxygen coverage differences between Pt, Pt0.9Rh0.1 and Pt0.9Ir0.1 microdiscs to predict the adsorption energy of these species on the Pt alloys and demonstrate a clear correlation between the metal activity towards the ORR and the charge associated with the reduction of the adsorbed oxygen species. In effect the coverage - adsorption energy relationship turns the charge associated with the reduction of the adsorbed oxygen species into a descriptor of the electrode activity towards the ORR. This study provides new insight into the oxygen reduction reaction and offers a new methodology to investigate low temperature fuel cell ORR catalysts. PMID:27021730

  8. Biocompatible reactive oxygen species (ROS)-responsive nanoparticles as superior drug delivery vehicles.

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    1996-11-01

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

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

    SciTech Connect

    Cassir, M.; Moutiers, G.; Devynck, J. . Lab d'Electrochimie)

    1993-11-01

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

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

    PubMed

    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. PMID:22509579

  12. Generation of reactive oxygen species and radiation response in lymphocytes and tumor cells.

    PubMed

    Shankar, Bhavani; Kumar, S Santosh; Sainis, K B

    2003-10-01

    Several types of lymphoid and myeloid tumor cells are known to be relatively resistant to radiation-induced apoptosis compared to normal lymphocytes. The intracellular generation of reactive oxygen species was measured in irradiated spleen cells from C57BL/6 and BALB/c mice and murine tumor cells (EL-4 and P388) by flow cytometry using dichlorodihydrofluoresceindiacetate and dihydrorhodamine 123 as fluorescent probes. The amount of reactive oxygen species generated per cell was low in the tumor cells compared to spleen cells exposed to 1 to 10 Gy of gamma radiation. This could be due to the higher total antioxidant levels in tumor cells compared to normal cells. Further, the changes in mitochondrial membrane potential and cytoplasmic Ca2+ content were appreciable in lymphocytes even at a dose of 1 Gy. In EL-4 cells, no such changes were observed at any of the doses used. About 65% of spleen cells underwent apoptosis 24 h after 1 Gy irradiation. However, under the same conditions, EL-4 and P388 cells failed to undergo apoptosis, but they accumulated in G2/M phase. Thus the intrinsic radioresistance of tumor cells may be due to a decreased generation of reactive oxygen species after irradiation and down-regulation of the subsequent events leading to apoptosis. PMID:12968927

  13. Tissue injury by reactive oxygen species and the protective effects of flavonoids.

    PubMed

    de Groot, H; Rauen, U

    1998-01-01

    Reactive oxygen species contribute decisively to a great variety of diseases. Flavonoids are benzo-gamma-pyrone derivatives of plant origin found in various fruits and vegetables but also in tea and in red wine. Some of the flavonoids, such as quercetin and silibinin, can effectively protect cells and tissues against the deleterious effects of reactive oxygen species. Their antioxidant activity results from scavenging of free radicals and other oxidizing intermediates, from the chelation of iron or copper ions and from inhibition of oxidases. For their free radical scavenging properties, scavenging of lipid- and protein-derived radicals is presumably of special importance. A non-radical reactive oxygen species effectively trapped by flavonoids is hypochlorous acid. In general, the antioxidative properties of flavonoids are favoured by a high degree of OH substitution. On the other hand, inhibition of enzymatic functions other than oxidases, e.g., inhibition of lipoxygenase and thus prevention of the formation of leukotrienes, may also participate in the cell and tissue protective properties of flavonoids. PMID:9646056

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

    PubMed

    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. PMID:26945820

  15. Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve

    PubMed Central

    Geng, Zhiwei; Tong, Xiaoyan; Jia, Hongjuan

    2015-01-01

    Non-freezing cold injury is an injury characterized by neuropathy, developing when patients expose to cold environments. Reactive oxygen species (ROS) has been shown as a contributing factor for the non-freezing cold nerve injury. However, the detailed connections between non-freezing cold nerve injury and ROS have not been described. In order to investigate the relationship between non-freezing cold nerve injury and reactive oxygen species, we study the effects of two cooling methods-the continuous cooling and the intermittent cooling with warming intervals-on rat sciatic nerves. Specifically, we assess the morphological changes and ROS production of the sciatic nerves underwent different cooling treatments. Our data shows both types of cooling methods cause nerve injury and ROS production. However, despite of identical cooling degree and duration, the sciatic nerves processed by intermittent cooling with warming intervals present more ROS production, severer reperfusion injury and pathological destructions than the sciatic nerves processed by continuous cooling. This result indicates reactive oxygen species, as a product of reperfusion, facilitates non-freezing cold nerve injury. PMID:26629065

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

    PubMed Central

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

    1997-01-01

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

  17. Influence of animal species on secondary oxidant activation in serum exposed to singlet oxygen.

    PubMed

    Lhommeau, Isabelle; Douillard, Samuel; Foursac, Antoine; Aillet, Lorena; Bigot, Edith; Patrice, Thierry

    2012-01-01

    Singlet oxygen ((1)O(2)) produced during inflammatory reactions and during photodynamic therapy deactivates by producing in tissues secondary reactive oxygen species and peroxides (SOS) as well as other degradation products. We investigated the influence of animal species on SOS production secondary to standardized (1)O(2) production by performing in vitro experiments with rose bengal as the (1)O(2) producer, human serum (HS) as a control, sera derived from various animal species, and dichloro-dihydro-fluorescein as a nonspecific marker that becomes fluorescent when oxidized. The overall SOS production in HS from a presumed healthy cohort of 53 donors (31 males and 22 females) gave a mean "normal" value of 0.91 compared with a previous pool of 75 male sera samples. SOS production after a photo-reaction was two or four times lower in HS than in fetal calf serum or mice sera, respectively. In mice, the "nude" characteristic increased even more than in the SOS production. In the Aves order, this production appeared to be distributed randomly according to the number of branches after the appearance of Amniotas. For primates, SOS production appeared to decrease linearly with the number of branches (R(2) = 0.98). Adding hemolysates from complete bloods to the corresponding sera induced an increase in SOS production in all species, proportional to the production in sera. These findings should be kept in mind when interpreting results from studies of secondary reactive oxygen species-induced pathways following (1)O(2) production, regardless of its origin. PMID:23382269

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

    PubMed Central

    Rossoni-Jnior, Joamyr Victor; Arajo, Glaucy Rodrigues; Pdua, Bruno da Cruz; Chaves, Mriam Martins; Pedrosa, Maria Lcia; Silva, Marcelo Eustquio; Costa, Daniela Caldeira

    2012-01-01

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

  19. Cross-Linking of Serine Racemase Dimer by Reactive Oxygen Species and Reactive Nitrogen Species

    PubMed Central

    Wang, Wei; Barger, Steven W.

    2011-01-01

    Serine racemase (SR) is the only identified enzyme in mammals responsible for isomerization of L-serine to D-serine, a co-agonist at NMDA receptors in the forebrain. Our previous data reported that an apparent SR dimer resistant to SDS and ?-mercaptoethanol was elevated in microglial cells after proinflammatory activation. Because the activation of microglia is typically associated with an oxidative burst, oxidative cross-linking between SR subunits was speculated. In this study, an siRNA technique was employed to confirm the identity of this SR dimer band. The oxidative species potentially responsible for the cross-linking was investigated with recombinant SR protein. The data indicate that nitric oxide, peroxynitrite, and hydroxyl radical were the likely candidates, while superoxide and hydrogen peroxide per se failed to contribute. Furthermore, the mechanism of formation of SR dimer by peroxynitrite oxidation was studied by mass spectrometry. A disulfide bond between Cys6 and Cys113 was identified in both SIN-1 treated SR monomer and dimer. Activity assays indicated that SIN-1 treatment decreased SR activity, confirming our previous conclusion that noncovalent dimer is the most active form of SR. These findings suggest a compensatory feedback whereby the consequences of neuroinflammation might dampen D-serine production to limit excitotoxic stimulation of NMDA receptors. PMID:22354542

  20. Inactivation effects of neutral reactive-oxygen species on Penicillium digitatum spores using non-equilibrium atmospheric-pressure oxygen radical source

    NASA Astrophysics Data System (ADS)

    Hashizume, Hiroshi; Ohta, Takayuki; Fengdong, Jia; Takeda, Keigo; Ishikawa, Kenji; Hori, Masaru; Ito, Masafumi

    2013-10-01

    The effectiveness of atomic and excited molecular oxygen species at inactivating Penicillium digitatum spores was quantitatively investigated by measuring these species and evaluating the spore inactivation rate. To avoid the effects of ultraviolet light and charged species, a non-equilibrium atmospheric-pressure radical source, which supplies only neutral radicals, was employed. Ground-state atomic oxygen (O(3Pj)) and excited molecular oxygen (O2(1Δg)) species were measured using vacuum ultraviolet absorption spectroscopy. The inactivation rate of spores was evaluated using the colony count method. The lifetimes of O(3Pj) and O2(1Δg) in an argon gas ambient at atmospheric pressure were found to be about 0.5 ms and much more than tens of ms, and their spore inactivation rates were about 10-17 cm3 s-1 and much lower than 10-21 cm3 s-1, respectively.

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

    PubMed Central

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  3. Controlling Reactive Oxygen and Nitrogen Species (RONS) Production by Atmospheric Pressure Plasma Jets Using Gas Shields

    NASA Astrophysics Data System (ADS)

    Norberg, Seth; Schmidt-Bleker, Ansgar; Winter, Jorn; Reuter, Stephan; Johnsen, Eric; Kushner, Mark J.

    2013-09-01

    Atmospheric pressure plasma jets are a source of reactive oxygen and nitrogen species (RONS) for many applications, including plasma medicine. A current challenge is to deliver RONS to surfaces in a controllable manner. One such control strategy is using gas shields around the plasma jet to minimize the generation of less desired RONS by preventing ambient gases from interacting with the plasma jet effluent. In this paper, we report on results of a computational investigation of the production of RONS from plasma jets into ambient air consisting of helium seeded with either N2 or O2 surrounded by a flowing gas shield and the flux of those species to a treated surface. The model used in this study, nonPDPSIM, solves transport equations for charged and neutral species, Poisson's equation, the electron energy equation for the electron temperature, and Navier-Stokes equations for the neutral gas flow. The shield gas has significant effects on unwanted RONS in the effluent of the plasma jet. N2 shield gas will minimize hydroxide and other reactive oxygen species in the effluent and to the surface. Similarly, O2 shield gas can reduce the production of nitric oxide and prevent the formation of other nitrogen compounds on the surface. Comparisons will be made to experimental measurements of optical emission from plasma jets using gas shields. Work supported by DOE Fusion Energy Science, NSF, BMBF.

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

    PubMed

    Chist, Renan Campos; Mercadante, Adriana Zerlotti; Gomes, Ana; Fernandes, Eduarda; Lima, Jos Lus Fontes da Costa; Bragagnolo, Neura

    2011-07-15

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

  5. Wolbachia Do Not Induce Reactive Oxygen Species-Dependent Immune Pathway Activation in Aedes albopictus

    PubMed Central

    Molloy, Jennifer C.; Sinkins, Steven P.

    2015-01-01

    Aedes albopictus is a major vector of dengue (DENV) and chikungunya (CHIKV) viruses, causing millions of infections annually. It naturally carries, at high frequency, the intracellular inherited bacterial endosymbiont Wolbachia strains wAlbA and wAlbB; transinfection with the higher-density Wolbachia strain wMel from Drosophila melanogaster led to transmission blocking of both arboviruses. The hypothesis that reactive oxygen species (ROS)-induced immune activation plays a role in arbovirus inhibition in this species was examined. In contrast to previous observations in Ae. aegypti, elevation of ROS levels was not observed in either cell lines or mosquito lines carrying the wild-type Wolbachia or higher-density Drosophila Wolbachia strains. There was also no upregulation of genes controlling innate immune pathways or with antioxidant/ROS-producing functions. These data suggest that ROS-mediated immune activation is not an important component of the viral transmission-blocking phenotype in this species. PMID:26287231

  6. Wolbachia Do Not Induce Reactive Oxygen Species-Dependent Immune Pathway Activation in Aedes albopictus.

    PubMed

    Molloy, Jennifer C; Sinkins, Steven P

    2015-08-01

    Aedes albopictus is a major vector of dengue (DENV) and chikungunya (CHIKV) viruses, causing millions of infections annually. It naturally carries, at high frequency, the intracellular inherited bacterial endosymbiont Wolbachia strains wAlbA and wAlbB; transinfection with the higher-density Wolbachia strain wMel from Drosophila melanogaster led to transmission blocking of both arboviruses. The hypothesis that reactive oxygen species (ROS)-induced immune activation plays a role in arbovirus inhibition in this species was examined. In contrast to previous observations in Ae. aegypti, elevation of ROS levels was not observed in either cell lines or mosquito lines carrying the wild-type Wolbachia or higher-density Drosophila Wolbachia strains. There was also no upregulation of genes controlling innate immune pathways or with antioxidant/ROS-producing functions. These data suggest that ROS-mediated immune activation is not an important component of the viral transmission-blocking phenotype in this species. PMID:26287231

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Kvietys, Peter R; Granger, D Neil

    2012-02-01

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

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

    PubMed Central

    Kvietys, Peter R.; Granger, D. Neil

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Mitochondrial production of reactive oxygen species: role of complex I and quinone analogues.

    PubMed

    Fato, Romana; Bergamini, Christian; Leoni, Serena; Lenaz, Giorgio

    2008-01-01

    Mitochondrial reactive oxygen species (ROS) are mainly produced by the respiratory chain enzymes. The sites for ROS production in mitochondrial respiratory chain are normally ascribed to the activity of Complex I and III. The presence of specific inhibitors modulates reactive oxygen species production in Complex I: inhibitors such as rotenone induce a strong ROS increase, while inhibitors such as stigmatellin prevent it. We have investigated the effect of hydrophilic quinones on Complex I ROS production in presence of different inhibitors. Some short chain quinones are Complex I inhibitors (CoQ2, idebenone and its derivatives), while CoQ1, decylubiquinone~ (DB) and duroquinone (DQ) are good electron acceptors from Complex I. Our results show that the ability of short chain quinones to induce an oxidative stress depends on the site of interaction with Complex I and on their physical-chemical characteristics. We can conclude that hydrophilic quinones may enhance oxidative stress by interaction with the electron escape sites on Complex I while more hydrophobic quinones can be reduced only at the physiological quinone reducing site without reacting with molecular oxygen. PMID:19096098

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

    PubMed Central

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

    2013-01-01

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

  13. Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes.

    PubMed

    DeAtley, S M; Aksenov, M Y; Aksenova, M V; Harris, B; Hadley, R; Cole Harper, P; Carney, J M; Butterfield, D A

    1999-02-01

    Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration. PMID:10211937

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

    SciTech Connect

    Chibli, H.; Carlini, L.; Park, S.; Dimitrijevic, N. M.; Nadeau, J. L.

    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.

  15. Photochemistry of Dissolved Black Carbon Released from Biochar: Reactive Oxygen Species Generation and Phototransformation.

    PubMed

    Fu, Heyun; Liu, Huiting; Mao, Jingdong; Chu, Wenying; Li, Qilin; Alvarez, Pedro J J; Qu, Xiaolei; Zhu, Dongqiang

    2016-02-01

    Dissolved black carbon (BC) released from biochar can be one of the more photoactive components in the dissolved organic matter (DOM) pool. Dissolved BC was mainly composed of aliphatics and aromatics substituted by aromatic C-O and carboxyl/ester/quinone moieties as determined by solid-state nuclear magnetic resonance. It underwent 56% loss of absorbance at 254 nm, almost complete loss of fluorescence, and 30% mineralization during a 169 h simulated sunlight exposure. Photoreactions preferentially targeted aromatic and methyl moieties, generating CH2/CH/C and carboxyl/ester/quinone functional groups. During irradiation, dissolved BC generated reactive oxygen species (ROS) including singlet oxygen and superoxide. The apparent quantum yield of singlet oxygen was 4.07 ± 0.19%, 2-3 fold higher than many well-studied DOM. Carbonyl-containing structures other than aromatic ketones were involved in the singlet oxygen sensitization. The generation of superoxide apparently depended on electron transfer reactions mediated by silica minerals in dissolved BC, in which phenolic structures served as electron donors. Self-generated ROS played an important role in the phototransformation. Photobleaching of dissolved BC decreased its ability to further generate ROS due to lower light absorption. These findings have significant implications on the environmental fate of dissolved BC and that of priority pollutants. PMID:26717492

  16. Structural studies on a low oxygen affinity hemoglobin from mammalian species: sheep (Ovis aries).

    PubMed

    Kamariah, Neelagandan; Ponnuraj, Sathya Moorthy; Moovarkumudalvan, Balasubramanian; Ponnuswamy, Mondikalipudur Nanjappa Gounder

    2014-07-18

    Hemoglobin (Hb) is in equilibrium between low affinity Tense (T) and high affinity Relaxed (R) states associated with its unliganded and liganded forms, respectively. Mammalian species can be classified into two groups on the basis of whether they express 'high' and 'low' oxygen affinity Hbs. Although Hbs from former group have been studied extensively, a limited number of structural studies have been performed for the low oxygen affinity Hbs. Here, the crystal structure of low oxygen affinity sheep methemoglobin (metHb) has been determined to 2.7 Å resolution. Even though sheep metHb adopts classical R state like quaternary structure, it shows localized quaternary and tertiary structural differences compared with other liganded Hb. The critical group of residues in the "joint region", shown as a major source of quaternary constraint on deoxyHb, formed unique interactions in the α1β2/α2β1 interfaces of sheep metHb structure. In addition, the constrained β subunits heme environment and the contraction of N-termini and A-helices of β subunits towards the molecular dyad are observed for sheep metHb structure. These observations provide the structural basis for a low oxygen affinity and blunt response to allosteric effector of sheep Hb. PMID:24858681

  17. Photochemical transformation of carboxylated multiwalled carbon nanotubes: role of reactive oxygen species.

    PubMed

    Qu, Xiaolei; Alvarez, Pedro J J; Li, Qilin

    2013-12-17

    The study investigated the photochemical transformation of carboxylated multiwalled carbon nanotubes (COOH-MWCNTs), an important environmental process affecting their physicochemical characteristics and hence fate and transport. UVA irradiation removed carboxyl groups from COOH-MWCNT surface while creating other oxygen-containing functional groups with an overall decrease in total surface oxygen content. This was attributed to reactions with photogenerated reactive oxygen species (ROS). COOH-MWCNTs generated singlet oxygen ((1)O2) and hydroxyl radical ((•)OH) under UVA light, which exhibited different reactivity toward the COOH-MWCNT surface. Inhibition experiments that isolate the effects of (•)OH and (1)O2 as well as experiments using externally generated (•)OH and (1)O2 separately revealed that (•)OH played an important role in the photochemical transformation of COOH-MWCNTs under UVA irradiation. The Raman spectroscopy and surface functional group analysis results suggested that (•)OH initially reacted with the surface carboxylated carbonaceous fragments, resulting in their degradation or exfoliation. Further reaction between (•)OH and the graphitic sidewall led to formation of defects including functional groups and vacancies. These reactions reduced the surface potential and colloidal stability of COOH-MWCNTs, and are expected to reduce their mobility in aquatic systems. PMID:24255932

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

    In flowering plants, sperm are transported inside pollen tubes to the female gametophyte for fertilization. The female gametophyte induces rupture of the penetrating pollen tube, resulting in sperm release and rendering them available for fertilization. Here we utilize the Arabidopsis FERONIA (FER) receptor kinase mutants, whose female gametophytes fail to induce pollen tube rupture, to decipher the molecular mechanism of this critical male-female interactive step. We show that FER controls the production of high levels of reactive oxygen species at the entrance to the female gametophyte to induce pollen tube rupture and sperm release. Pollen tube growth assays in vitro and in the pistil demonstrate that hydroxyl free radicals are likely the most reactive oxygen molecules, and they induce pollen tube rupture in a Ca2+-dependent process involving Ca2+ channel activation. Our results provide evidence for a RHO GTPase-based signalling mechanism to mediate sperm release for fertilization in plants.

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

    PubMed

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

    2014-01-01

    In flowering plants, sperm are transported inside pollen tubes to the female gametophyte for fertilization. The female gametophyte induces rupture of the penetrating pollen tube, resulting in sperm release and rendering them available for fertilization. Here we utilize the Arabidopsis FERONIA (FER) receptor kinase mutants, whose female gametophytes fail to induce pollen tube rupture, to decipher the molecular mechanism of this critical male-female interactive step. We show that FER controls the production of high levels of reactive oxygen species at the entrance to the female gametophyte to induce pollen tube rupture and sperm release. Pollen tube growth assays in vitro and in the pistil demonstrate that hydroxyl free radicals are likely the most reactive oxygen molecules, and they induce pollen tube rupture in a Ca(2+)-dependent process involving Ca(2+) channel activation. Our results provide evidence for a RHO GTPase-based signalling mechanism to mediate sperm release for fertilization in plants. PMID:24451849

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

    dickinson, Bryan C; Chang, Christopher J

    2012-01-01

    Reactive oxygen species (ROS) are a family of molecules that are continuously generated, transformed and consumed in all living organisms as a consequence of aerobic life. The traditional view of these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease. However, emerging data show that ROS produced in certain situations can also contribute to physiology and increased fitness. This Perspective provides a focused discussion on what factors lead ROS molecules to become signal and/or stress agents, highlighting how increasing knowledge of the underlying chemistry of ROS can lead to advances in understanding their disparate contributions to biology. An important facet of this emerging area at the chemistry-biology interface is the development of new tools to study these small molecules and their reactivity in complex biological systems. PMID:21769097

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

    PubMed

    Bernhard, Joan M; Bowser, Samuel S

    2008-01-01

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

  3. Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro.

    PubMed

    Bonnefont-Rousselot, Dominique; Collin, Fabrice; Jore, Daniel; Gardès-Albert, Monique

    2011-04-01

    Melatonin (N-acetyl-5-hydroxytryptamine) is a pineal hormone widely known for its antioxidant properties, both in vivo and by direct capture of free radicals in vitro. Although some metabolites and oxidation products of melatonin have been identified, the molecular mechanism by which melatonin exerts its antioxidant properties has not been totally unravelled. This study investigated the reaction mechanism of oxidation of melatonin by radio-induced reactive oxygen species, generated by gamma radiolysis of water for aqueous solutions of melatonin (from 20 to 200 μm), in the presence or absence of molecular oxygen. The hydroxyl radical was found to be the unique species able to initiate the oxidation process, leading to three main products, e.g. N(1)-acetyl-N(2)-formyl-5-methoxykynurenin (AFMK), N(1)-acetyl-5-methoxykynurenin (AMK) and hydroxymelatonin (HO-MLT). The generation of AFMK and HO-MLT strongly depended on the presence of molecular oxygen in solution: AFMK was the major product in aerated solutions (84%), whereas HO-MLT was favoured in the absence of oxygen (86%). Concentrations of AMK remained quite low, and AMK was proposed to result from a chemical hydrolysis of AFMK in solution. A K-value of 1.1 × 10(-4) was calculated for this equilibrium. Both hydrogen peroxide and superoxide dismutase had no effect on the radio-induced oxidation of melatonin, in good accordance for the second case with the poor reactivity of the superoxide anion towards melatonin. Finally, a reaction mechanism was proposed for the oxidation of melatonin in vitro. PMID:21244479

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

    EPA Science Inventory

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

  5. Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction

    PubMed Central

    Weidinger, Adelheid; Kozlov, Andrey V.

    2015-01-01

    In the past, reactive oxygen and nitrogen species (RONS) were shown to cause oxidative damage to biomolecules, contributing to the development of a variety of diseases. However, recent evidence has suggested that intracellular RONS are an important component of intracellular signaling cascades. The aim of this review was to consolidate old and new ideas on the chemical, physiological and pathological role of RONS for a better understanding of their properties and specific activities. Critical consideration of the literature reveals that deleterious effects do not appear if only one primary species (superoxide radical, nitric oxide) is present in a biological system, even at high concentrations. The prerequisite of deleterious effects is the formation of highly reactive secondary species (hydroxyl radical, peroxynitrite), emerging exclusively upon reaction with another primary species or a transition metal. The secondary species are toxic, not well controlled, causing irreversible damage to all classes of biomolecules. In contrast, primary RONS are well controlled (superoxide dismutase, catalase), and their reactions with biomolecules are reversible, making them ideal for physiological/pathophysiological intracellular signaling. We assume that whether RONS have a signal transducing or damaging effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity. PMID:25884116

  6. Functional implications of mitochondrial reactive oxygen species generated by oncogenic viruses

    PubMed Central

    Choi, Young Bong; Harhaj, Edward William

    2014-01-01

    Between 15–20% of human cancers are associated with infection by oncogenic viruses. Oncogenic viruses, including HPV, HBV, HCV and HTLV-1, target mitochondria to influence cell proliferation and survival. Oncogenic viral gene products also trigger the production of reactive oxygen species which can elicit oxidative DNA damage and potentiate oncogenic host signaling pathways. Viral oncogenes may also subvert mitochondria quality control mechanisms such as mitophagy and metabolic adaptation pathways to promote virus replication. Here, we will review recent progress on viral regulation of mitophagy and metabolic adaptation and their roles in viral oncogenesis. PMID:25580106

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

    PubMed

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

    2014-10-15

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

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

    PubMed

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

    2003-05-01

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

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

    PubMed

    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 colonies 24h after the usual, colony-wide feeding. At this time, a single polyp was fed, and this polyp was compared with an otherwise similar polyp from the same colony. A pattern similar to the whole-colony experiments was obtained: the just-fed polyp, as it begins contracting shortly after feeding, appears to be relatively oxidized, with low levels of peroxide compared with the polyp that was not fed. These data are consistent with the hypothesis that adaptive colony development in response to a variable food supply is mediated by redox state or reactive oxygen species or both, although alternative hypotheses are also discussed. PMID:11441027

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

    PubMed Central

    Nathan, Carl; Cunningham-Bussel, Amy

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  12. Activity of artichoke leaf extract on reactive oxygen species in human leukocytes.

    PubMed

    Pérez-García, F; Adzet, T; Cañigueral, S

    2000-11-01

    Artichoke leaf extract was studied in human leukocytes for activity against oxidative stress using flow cytometry and dichlorofluorescin diacetate as a fluorescence probe. It produces a concentration-dependent inhibition of oxidative stress when cells are stimulated with agents that generate reactive oxygen species (ROS): hydrogen peroxide, phorbol-12-myristate-13-acetate (PMA), and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Cynarin, caffeic acid, chlorogenic acid, and luteolin, constituents of artichoke leaf extract, also show a concentration-dependent inhibitory activity in the above models, contributing to the antioxidant activity of the extract in human neutrophils. PMID:11200096

  13. Elevated Cytoplasmic Free Zinc and Increased Reactive Oxygen Species Generation in the Context of Brain Injury.

    PubMed

    Stork, Christian J; Li, Yang V

    2016-01-01

    Intracellular zinc release and the generation of reactive oxygen species (ROS) have been reported to be common ingredients in numerous toxic signaling mechanisms in neurons. A key source for intracellular zinc release is its liberation from metallothionein-III (MT-III). MT-III binds and regulates intracellular zinc levels under physiological conditions, but the zinc-binding thiols readily react with certain ROS and reactive nitrogen species (RNS) to result in intracellular zinc liberation. Liberated zinc induces ROS and RNS generation by multiple mechanisms, including the induction of mitochondrial ROS production, and also promotes ROS formation outside the mitochondria by interaction with the enzymes NADPH oxidase and 12-lipoxygenase. Of particular relevance to neuronal injury in the context of ischemia and prolonged seizures, the positive feedback cycle between ROS/RNS generation and increasing zinc liberation will be examined. PMID:26463973

  14. Exceedingly Fast Oxygen Atom Transfer to Olefins via a Catalytically Competent Nonheme Iron Species.

    PubMed

    Serrano-Plana, Joan; Aguinaco, Almudena; Belda, Raquel; García-España, Enrique; Basallote, Manuel G; Company, Anna; Costas, Miquel

    2016-05-17

    The reaction of [Fe(CF3 SO3 )2 (PyNMe3 )] with excess peracetic acid at -40 °C leads to the accumulation of a metastable compound that exists as a pair of electromeric species, [Fe(III) (OOAc)(PyNMe3 )](2+) and [Fe(V) (O)(OAc)(PyNMe3 )](2+) , in fast equilibrium. Stopped-flow UV/Vis analysis confirmed that oxygen atom transfer (OAT) from these electromeric species to olefinic substrates is exceedingly fast, forming epoxides with stereoretention. The impact of the electronic and steric properties of the substrate on the reaction rate could be elucidated, and the relative reactivities determined for the catalytic oxidations could be reproduced by kinetic studies. The observed fast reaction rates and high selectivities demonstrate that this metastable compound is a truly competent OAT intermediate of relevance for nonheme iron catalyzed epoxidations. PMID:27071372

  15. Investigation of a sterilization system using active oxygen species generated by ultraviolet irradiation.

    PubMed

    Yoshino, Kiyoshi; Matsumoto, Hiroyuki; Iwasaki, Tatsuyuki; Kinoshita, Shinobu; Noda, Kazutoshi; Oya, Kei; Iwamori, Satoru

    2015-01-01

    We have been investigating an advanced sterilization system that employs active oxygen species (AOS). We designed the sterilization equipment, including an evacuation system, which generates AOS from pure oxygen gas using ultraviolet irradiation, in order to study the conditions necessary for sterilization in the system's chamber. Using Geobachillus stearothermophilus spores (10(6) CFU) in a sterile bag as a biological indicator (BI) in the chamber of the AOS sterilization apparatus, we examined the viability of the BI as a function of exposure time, assessing the role of the decompression level in the sterilization performance. We found that the survival curves showed exponential reduction, and that the decompression level did not exert a significant influence on the survival curve. Subsequently, we investigated the sterilization effect as influenced by the spatial and environmental temperature variation throughout the chamber, and found that the sterilization effect varied with position, due to the varying environmental temperature in the respective areas. We confirmed that temperature is one of the most important factors influencing sterilization in the chamber, and estimated the temperature effect on the distribution of atomic oxygen concentration, using the quartz crystal microbalance (QCM) method with fluorocarbon thin film prepared by radio frequency sputtering. PMID:25817808

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

    PubMed Central

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

    2011-01-01

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

  17. [Microcirculatory hemodynamics in oral tissues with reference to neurogenic response and reactive oxygen species interaction].

    PubMed

    Okabe, E; Todoki, K

    1999-04-01

    The primary purpose of the microcirculation is to transport nutrients and oxygen and to remove metabolic waste products from tissues. It is also well known that the fundamental mechanism for vascular control is the local regulation of the basal vascular tone, which is reinforced by blood pressure and counteracted by tissue metabolites. Thus, the well-being of the tissue depends on the circulatory transport process, which is governed by many functional parameters of the microcirculation such as blood flow, blood volume, intravascular and extravascular pressures, and capillary permeability. Inflammatory reactions in oral tissues can be initiated by many different insults to the tissues, and the reaction itself can be expressed in various ways. In addition, the tissues seem to have many "backup" systems, so that any one response can be produced in several ways, which is important for a reaction that has a survival value. A recent concept is that repeated stimulation of sensitive teeth may induce pulpal changes; this could occur through induction of neurogenic inflammation and alteration of pulpal blood flow. One possibility is that production of reactive oxygen species, as well as release of the sensory neuropeptides, at sites of inflammation contributes to alterations in local blood flow. In addition to the part played by the neurogenic mediators, nitric oxide participation and its interaction with oxygen-derived free radicals in oral tissue hemodynamics are also discussed. PMID:10412160

  18. Reactive oxygen species are partially involved in the bacteriocidal action of hypochlorous acid.

    PubMed

    Dukan, S; Belkin, S; Touati, D

    1999-07-15

    Hypochlorous acid (HOCl) is probably the most widely used disinfectant worldwide and has an important role in inflammatory reaction and in human resistance to infection. However, the nature and mechanisms of its bactericidal activity are still poorly understood. Bacteria challenged aerobically with HOCl concentrations ranging from 9.5 to 76 microM exhibit higher ability to form colonies anaerobically than aerobically. Conversely, aerobic plating greatly increased lethality after an anaerobic HOCl challenge, although anaerobic survival did not depend on whether HOCl exposure was aerobic or anaerobic. Even a short transient exposure to air after anaerobic HOCl challenge reduced anaerobic survival, indicative of immediate deleterious effects of oxygen. Exposure to HOCl can cause lethal DNA damage as judged by the fact that recA sensitivity to HOCl was oxygen dependent. Antioxidant defenses such as reduced glutathione and glucose-6-phosphate dehydrogenase were depleted or inactivated at 10 microM HOCl, while other activities, such as superoxide dismutase, dropped only above 57 microM HOCl. Cumulative deficiencies in superoxide dismutase and glucose-6-phosphate dehydrogenase rendered strains hypersensitive to HOCl. This indicates that part of HOCl toxicity on Escherichia coli is mediated by reactive oxygen species during recovery. PMID:10395749

  19. Copper elevated embryonic hemoglobin through reactive oxygen species during zebrafish erythrogenesis.

    PubMed

    Zhou, Xin-Ying; Zhang, Ting; Ren, Long; Wu, Jun-Jie; Wang, Weimin; Liu, Jing-Xia

    2016-06-01

    Copper, as an essential trace mineral, can cause diseases such as childhood leukemia at excess levels, but has been applied in anemia therapy for a long time. However, few reports have studied its role during hematopoiesis at the molecular level in an animal model. In this study, by microarray, qRT-PCR, whole-mount in situ hybridization and O-dianisidine staining detections, we revealed the increased expression of hemoglobin in copper-exposed embryos. Secondly, we found that copper-exposed embryos exhibited high levels of reactive oxygen species (ROS), and genes in oxygen binding and oxygen transporting were up-regulated in the embryos. Finally, we found that ROS scavengers NAC, GSH, and DMTU not only inhibited in vivo ROS levels induced by copper, but also significantly decreased high expression of hemoglobin back to almost normal levels in copper exposed embryos, and also helped with copper elimination from the embryos. Our data first demonstrated that ROS mediated copper induced hemoglobin expression in vertebrates, partly revealing the underlying molecular mechanism of copper therapy for anemia. Moreover, we revealed that copper homeostasis was broken by its induced ROS and ROS helped with copper overloading in the body, which could be applied as a novel therapy target for copper-caused diseases. PMID:26991749

  20. Mitochondrial free radical overproduction due to respiratory chain impairment in the brain of a mouse model of Rett syndrome: protective effect of CNF1.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; de Bari, Lidia; De Rasmo, Domenico; Musto, Mattia; Fabbri, Alessia; Ricceri, Laura; Fiorentini, Carla; Laviola, Giovanni; Vacca, Rosa Anna

    2015-06-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors. Its pathogenesis remains mostly not understood and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of the oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, a condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice seems mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as an energy source. Respiratory chain impairment is brain area specific, owing to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioral phenotype and brain bioenergetic markers in an RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality, and the prevention of brain hydrogen peroxide overproduction. These results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and highlight CNF1 efficacy in counteracting RTT-related mitochondrial defects. PMID:25708779

  1. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome.

    PubMed

    Cruz, Josiane C; Flôr, Atalia F L; França-Silva, Maria S; Balarini, Camille M; Braga, Valdir A

    2015-01-01

    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. PMID:26779026

  2. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome

    PubMed Central

    Cruz, Josiane C.; Flôr, Atalia F. L.; França-Silva, Maria S.; Balarini, Camille M.; Braga, Valdir A.

    2015-01-01

    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. PMID:26779026

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

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

    2008-05-15

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

  5. Gastric toxicity and mucosal ulceration induced by oxygen-derived reactive species: protection by melatonin.

    PubMed

    Bandyopadhyay, D; Biswas, K; Bhattacharyya, M; Reiter, R J; Banerjee, R K

    2001-09-01

    Uncontrolled hydrochloric acid secretion and ulceration of the stomach mucosa due to various factors are serious global problems. Although the mechanism of acid secretion from the parietal cell is now well understood, the processes involved in gastric ulceration are still not clear. Among various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori infection and due to use of nonsteroidal antiinflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species, especially the hydroxyl radical. A number of excellent drugs have proven useful in controlling hyperacidity and ulceration but their long-term use is associated with disturbing side-effects. Hence, the search is still on to find a compound possessing antisecretory, antiulcer and antioxidant properties which will serve as a therapeutic agent to reduce gastric hyperacidity and ulcers. This article describes the role of reactive oxygen species in gastric ulceration, drugs controlling them with their merits and demerits and, the role of melatonin, a pineal secretory product, in protecting against gastric lesions. In experimental studies, melatonin has been shown to be effective in reducing mucosal breakdown and ulcer formation in a wide variety of situations. Additionally, the low toxicity of melatonin supports further investigation of this molecule as a gastroprotective agent. Finally, we include a commentary on how melatonin research with respect to gastric pathophysiology can move forward with a view of eventually using this indole as a therapeutic agent to control gastric ulceration in humans. PMID:11899094

  6. Involvement of reactive oxygen species in gastric ulceration: protection by melatonin.

    PubMed

    Bandyopadhyay, Debashis; Biswas, Kaushik; Bhattacharyya, Mrinalini; Reiter, Russel J; Banerjee, Ranajit K

    2002-06-01

    Uncontrolled hydrochloric acid secretion and ulceration in the stomach due to various factors are serious global problems today. Although the mechanism of acid secretion from the parietal cell is now fairly known, the mechanism of gastric ulceration is still not clear today. Among various causes of gastric ulceration, lesions caused by stress, alcohol consumption, Helicobacter pylori infection and use of nonsteroidal antiinflammatory drugs have been shown to be mediated largely through the generation of reactive oxygen species especially hydroxyl radical (*OH). A number of excellent drugs have been proved useful in controlling hyperacidity and ulceration but their long term uses are not devoid of disturbing side-effects. Hence, the search is still on to find out a compound possessing antisecretory, antiulcer and antioxidant properties which will serve as a powerful therapeutic agent to cure gastric hyperacidity and ulcer. This article describes the role of reactive oxygen species in gastric ulceration, drugs controlling them with their merits and demerits and, the role of melatonin, a pineal hormone in protecting the gastric lesions with a final commentary on how melatonin research with respect to gastric pathophysiology can be taken forward with a view to projecting this indole as a promising therapeutic agent to control gastric ulceration in humans. PMID:12587717

  7. The Role of Reactive Oxygen Species in Mesenchymal Stem Cell Adipogenic and Osteogenic Differentiation: A Review

    PubMed Central

    Atashi, Fatemeh; Modarressi, Ali

    2015-01-01

    Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs. PMID:25603196

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

    PubMed Central

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

    2014-01-01

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

  9. Extensive Dark Biological Production of Reactive Oxygen Species in Brackish and Freshwater Ponds.

    PubMed

    Zhang, Tong; Hansel, Colleen M; Voelker, Bettina M; Lamborg, Carl H

    2016-03-15

    Within natural waters, photodependent processes are generally considered the predominant source of reactive oxygen species (ROS), a suite of biogeochemically important molecules. However, recent discoveries of dark particle-associated ROS production in aquatic environments and extracellular ROS production by various microorganisms point to biological activity as a significant source of ROS in the absence of light. Thus, the objective of this study was to explore the occurrence of dark biological production of the ROS superoxide (O2(-)) and hydrogen peroxide (H2O2) in brackish and freshwater ponds. Here we show that the ROS superoxide and hydrogen peroxide were present in dark waters at comparable concentrations as in sunlit waters. This suggests that, at least for the short-lived superoxide species, light-independent processes were an important control on ROS levels in these natural waters. Indeed, we demonstrated that dark biological production of ROS extensively occurred in brackish and freshwater environments, with greater dark ROS production rates generally observed in the aphotic relative to the photic zone. Filtering and formaldehyde inhibition confirmed the biological nature of a majority of this dark ROS production, which likely involved phytoplankton, particle-associated heterotrophic bacteria, and NADH-oxidizing enzymes. We conclude that biological ROS production is widespread, including regions devoid of light, thereby expanding the relevance of these reactive molecules to all regions of our oxygenated global habit. PMID:26854358

  10. Candida albicans biofilms do not trigger reactive oxygen species and evade neutrophil killing.

    PubMed

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

    2012-12-15

    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

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

    PubMed

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

    2012-10-01

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

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

    PubMed Central

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

    2013-01-01

    Cyanide-resistant non-phosphorylating respiration is known in mitochondria from plants, fungi, and microorganisms but is absent in mammals. It results from the activity of an alternative oxidase (AOX) that conveys electrons directly from the respiratory chain (RC) ubiquinol pool to oxygen. AOX thus provides a bypath that releases constraints on the cytochrome pathway and prevents the over-reduction of the ubiquinone pool, a major source of superoxide. RC dysfunctions and deleterious superoxide overproduction are recurrent themes in human pathologies, ranging from neurodegenerative diseases to cancer, and may be instrumental in ageing. Thus, preventing RC blockade and excess superoxide production by means of AOX should be of considerable interest. However, because of its energy-dissipating properties, AOX might produce deleterious effects of its own in mammals. Here we show that AOX can be safely expressed in the mouse (MitAOX), with major physiological parameters being unaffected. It neither disrupted the activity of other RC components nor decreased oxidative phosphorylation in isolated mitochondria. It conferred cyanide-resistance to mitochondrial substrate oxidation and decreased reactive oxygen species (ROS) production upon RC blockade. Accordingly, AOX expression was able to support cyanide-resistant respiration by intact organs and to afford prolonged protection against a lethal concentration of gaseous cyanide in whole animals. Taken together, these results indicate that AOX expression in the mouse is innocuous and permits to overcome a RC blockade, while reducing associated oxidative insult. Therefore, the MitAOX mice represent a valuable tool in order to investigate the ability of AOX to counteract the panoply of mitochondrial-inherited diseases originating from oxidative phosphorylation defects. PMID:23300486

  13. Oxygen consumption and thermoregulatory responses in three species of South American marsupials.

    PubMed

    Ribeiro, Marcel Cintra Pereira; Bicudo, José Eduardo Pereira Wilken

    2007-07-01

    Oxygen consumption (VO(2)), body temperature (T(b)) and wet thermal conductance (C(wet)), under resting conditions, exposure to low ambient temperature (T(a)) and during sustained exercise (treadmill running) were measured in three phylogenetic related (same family; Didelphidae) South American marsupials possessing similar body masses: Caluromys philander (arboreal/fruit and insect eating), Philander opossum (terrestrial and arboreal/omnivore), and Metachirus nudicaudatus (terrestrial/omnivore). Our measurements of VO(2) and C(wet) under resting conditions agree with those previously reported for other marsupials. We expected that C. philander would show a lower maximal sustained VO(2), compared to the other two species, based on its more reduced skeletal muscle mass. However, the values obtained for C. philander were not statistically different (ANOVA) from those obtained for the other two species. When exposed to low ambient temperature (12 degrees C), differences among the three species were detected, i.e., M. nudicaudatus did not survive, while the other two species were able to reduce their T(b) under such conditions. C. philander gradually decreases its T(b) when cold exposed, and P. opossum shows a more pronounced T(b) drop only when exposure to low ambient temperatures occurs for a more prolonged period of time. PMID:17020814

  14. Warm acclimation and oxygen depletion induce species-specific responses in salmonids.

    PubMed

    Anttila, Katja; Lewis, Mario; Prokkola, Jenni M; Kanerva, Mirella; Seppänen, Eila; Kolari, Irma; Nikinmaa, Mikko

    2015-05-15

    Anthropogenic activities are greatly altering the habitats of animals, whereby fish are already encountering several stressors simultaneously. The purpose of the current study was to investigate the capacity of fish to respond to two different environmental stressors (high temperature and overnight hypoxia) separately and together. We found that acclimation to increased temperature (from 7.7±0.02°C to 14.9±0.05°C) and overnight hypoxia (daily changes from normoxia to 63-67% oxygen saturation), simulating climate change and eutrophication, had both antagonistic and synergistic effects on the capacity of fish to tolerate these stressors. The thermal tolerance of Arctic char (Salvelinus alpinus) and landlocked salmon (Salmo salar m. sebago) increased with warm acclimation by 1.3 and 2.2°C, respectively, but decreased when warm temperature was combined with overnight hypoxia (by 0.2 and 0.4°C, respectively). In contrast, the combination of the stressors more than doubled hypoxia tolerance in salmon and also increased hypoxia tolerance in char by 22%. Salmon had 1.2°C higher thermal tolerance than char, but char tolerated much lower oxygen levels than salmon at a given temperature. The changes in hypoxia tolerance were connected to the responses of the oxygen supply and delivery system. The relative ventricle mass was higher in cold- than in warm-acclimated salmon but the thickness of the compact layer of the ventricle increased with the combination of warm and hypoxia acclimation in both species. Char had also significantly larger hearts and thicker compact layers than salmon. The results illustrate that while fish can have protective responses when encountering a single environmental stressor, the combination of stressors can have unexpected species-specific effects that will influence their survival capacity. PMID:25827840

  15. Detection of irradiation induced reactive oxygen species production in live cells

    NASA Astrophysics Data System (ADS)

    Gao, Bo; Zhu, Debin

    2006-09-01

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

  16. Reactive Oxygen Species and Induction of Lignin Peroxidase in Phanerochaete chrysosporium

    PubMed Central

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

    2003-01-01

    We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O2) of Phanerochaete chrysosporium by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O2 gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O2 (oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O2 concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O2 is at least partially mediated by the intracellular ROS. PMID:14602606

  17. Oxygen-assisted reduction of Au species on Au/SiO2 catalyst in room temperature CO oxidation

    SciTech Connect

    Wu, Zili; Zhou, Shenghu; Zhu, Haoguo; Dai, Sheng; Overbury, Steven {Steve} H

    2008-01-01

    An unexpected oxygen-assisted reduction of cationic Au species by CO was found on a Au/SiO2 catalyst at room temperature; CO oxidation activity increases simultaneously with the reduction of Au species, suggesting the key role of metallic Au played in CO oxidation on Au/SiO2.

  18. Evaluation of multistep derivatization methods for identification and quantification of oxygenated species in organic aerosol.

    PubMed

    Flores, Rosa M; Doskey, Paul V

    2015-10-30

    Two, 3-step methods for derivatizing mono- and multi-functional species with carbonyl (CO), carboxylic acid (-COOH), and alcohol (-OH) moieties were compared and optimized. In Method 1, the CO, -COOH, and -OH moieties were converted (1) to methyloximes (R-CN-OCH3) with O-methylhydroxylamine hydrochloride (MHA), (2) to methyl esters (OC-R-OCH3) with (trimethylsilyl)diazomethane in methanol (TMSD/MeOH), and (3) to trimethylsilyl ethers [R-OSi(CH3)3] with N,O-bis(trimethylsilyl)-trifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane (TMCS), respectively. Steps 1 and 3 of both methods were identical; however, in Step 2 of Method 2, -COOH moieties were derivatized with 10% (v/v) boron trifluoride (BF3) in MeOH or n-butanol (n-BuOH). The BF3/MeOH and BF3/n-BuOH were ineffective at converting species with more than 2-OH moieties. Average standard deviations for derivatization of 36 model compounds by the 3-step methods using TMSD/MeOH and BF3/(MeOH) were 7.4 and 14.8%, respectively. Average derivatization efficiencies for Methods 1 and 2 were 88.0 and 114%, respectively. Despite the lower average derivatization efficiency of Method 1, distinct advantages included a greater certainty of derivatization yield for the entire suite of mono- and multi-functional species and fewer processing steps for sequential derivatization. Detection limits for Method 1 using GCGC-ToF-MS were 0.3-54pgm(-3). Approximately 100 oxygenated organic species were identified and quantified in aerosol filtered from 39m(3) of air in an urban location. Levels of species were 0.013-17ngm(-3) and were nearly all above the Method 1 limit of detection. PMID:26427323

  19. Metabolism of reactive oxygen species and reactive nitrogen species in pepper (Capsicum annuum L.) plants under low temperature stress.

    PubMed

    Airaki, Morad; Leterrier, Marina; Mateos, Rosa M; Valderrama, Raquel; Chaki, Mounira; Barroso, Juan B; Del Río, Luis A; Palma, José M; Corpas, Francisco J

    2012-02-01

    Low temperature is an environmental stress that affects crop production and quality and regulates the expression of many genes, and the level of a number of proteins and metabolites. Using leaves from pepper (Capsicum annum L.) plants exposed to low temperature (8 °C) for different time periods (1 to 3 d), several key components of the metabolism of reactive nitrogen and oxygen species (RNS and ROS, respectively) were analysed. After 24 h of exposure at 8 °C, pepper plants exhibited visible symptoms characterized by flaccidity of stems and leaves. This was accompanied by significant changes in the metabolism of RNS and ROS with an increase of both protein tyrosine nitration (NO(2) -Tyr) and lipid peroxidation, indicating that low temperature induces nitrosative and oxidative stress. During the second and third days at low temperature, pepper plants underwent cold acclimation by adjusting their antioxidant metabolism and reverting the observed nitrosative and oxidative stress. In this process, the levels of the soluble non-enzymatic antioxidants ascorbate and glutathione, and the activity of the main NADPH-generating dehydrogenases were significantly induced. This suggests that ascorbate, glutathione and the NADPH-generating dehydrogenases have a role in the process of cold acclimation through their effect on the redox state of the cell. PMID:21414013

  20. Reactive oxygen species in plasma against E. coli cells survival rate

    NASA Astrophysics Data System (ADS)

    Zhou, Ren-Wu; Zhang, Xian-Hui; Zong, Zi-Chao; Li, Jun-Xiong; Yang, Zhou-Bin; Liu, Dong-Ping; Yang, Si-Ze

    2015-08-01

    In this paper, we report on the contrastive analysis of inactivation efficiency of E. coli cells in solution with different disinfection methods. Compared with the hydrogen peroxide solution and the ozone gas, the atmospheric-pressure He plasma can completely kill the E. coli cells in the shortest time. The inactivation efficiency of E. coli cells in solution can be well described by using the chemical reaction rate model. X-ray photoelectron spectroscopy (XPS) analysis shows that the C-O or C=O content of the inactivated E. coli cell surface by plasma is predominantly increased, indicating the quantity of oxygen-containing species in plasma is more than those of two other methods, and then the C-C or C-H bonds can be broken, leading to the etching of organic compounds. Analysis also indicates that plasma-generated species can play a crucial role in the inactivation process by their direct reactions or the decompositions of reactive species, such as ozone into OH radicals in water, then reacting with E. coli cells. Project supported by the Natural Science Foundation of Fujian Province, China (Grant No. 2014J01025), the National Natural Science Foundation of China (Grant No. 11275261), and the Funds from the Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance, China.

  1. Emission of short-chained oxygenated voc from the leaves of mature central european tree species

    NASA Astrophysics Data System (ADS)

    Kreuzwieser, J.; Cojocariu, C.; Rennenberg, H.

    2003-04-01

    The photolytic and oxidative destruction of volatile organic compounds (VOC) in the atmosphere results in a net production of tropospheric ozone. Oxygenated VOC (OVOC) are either directly emitted into the atmosphere or are produced there by oxidation of other hydrocarbons. Besides anthropogenic sources, the emission of OVOC by vegetation, particularly by forest ecosystems, is considered a major source of atmospheric OVOC. Exact numbers on emission rates from important tree species as well as production mechanisms that lead to the release of OVOC from leaves are, however, not known. In the present study, field campaigns were conducted in typical forest ecosystems in Germany in order to elucidate the spectrum and the amount of OVOC emitted by Central European tree species. Exchange data obtained were compared with physiological and meteorological parameters to obtain information on the factors controlling trace gas exchange. The field campaigns were accompanied by studies under controlled conditions in the laboratory. The poster presents data on carbonyl exchange between Picea abies, Fagus sylvatica, Carpinus betulus and other species and the atmosphere and indicates plant internal and meteorological factors (temperature, ambient OVOC concentrations, light intensities, water supply, etc.) that may determine exchange rates.

  2. A novel biointerface that suppresses cell morphological changes by scavenging excess reactive oxygen species.

    PubMed

    Ikeda, Yutaka; Yoshinari, Tomoki; Nagasaki, Yukio

    2015-09-01

    During cell cultivation on conventional culture dishes, various events results in strong stresses that lead to the production of bioactive species such as reactive oxygen species (ROS) and nitric oxide. These reactive species cause variable damage to cells and stimulate cellular responses. Here, we report the design of a novel biocompatible surface that decreases stress by not only morphologically modifying the dish surface by using poly(ethylene glycol) tethered chains, but also actively scavenging oxidative stress by using our novel nitroxide radical-containing polymer. A block copolymer, poly(ethylene glycol)-b-poly[(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PEG-b-PMNT) was used to coat the surface of a dish. Differentiation of undifferentiated human leukemia (HL-60) cells was found to be suppressed on the polymer-coated dish. Notably, HL-60 cell cultivation caused apoptosis under high-density conditions, while spontaneous apoptosis was suppressed in cells plated on the PEG-b-PMNT-modified surface, because a healthy mitochondrial membrane potential was maintained. In contrast, low molecular weight antioxidants did not have apparent effects on the maintenance of mitochondria. We attribute this to the lack of cellular internalization of our immobilized polymer and selective scavenging of excessive ROS generated outside of cells. These results demonstrate the utility of our novel biocompatible material for actively scavenging ROS and thus maintaining cellular morphology. PMID:25691268

  3. Relationship between Active Oxygen Species, Lipid Peroxidation, Necrosis, and Phytoalexin Production Induced by Elicitins in Nicotiana.

    PubMed Central

    Rusterucci, C.; Stallaert, V.; Milat, M. L.; Pugin, A.; Ricci, P.; Blein, J. P.

    1996-01-01

    Excised leaves of Nicotiana tabacum var Xanthi and Nicotiana rustica were treated with cryptogein and capsicein, basic and acidic elicitins, respectively. Both compounds induced leaf necrosis, the intensity of which depended on concentration and duration of treatment. N. tabacum var Xanthi was the most sensitive species and cryptogein was the most active elicitin. Lipid peroxidation in elicitin-treated Nicotiana leaves was closely correlated with the appearance of necrosis. Elicitin treatments induced a rapid and transient burst of active oxygen species (AOS) in cell cultures of both Nicotiana species, with the production by Xanthi cells being 6-fold greater than that by N. rustica. Similar maximum AOS production levels were observed with both elicitins, but capsicein required 10-fold higher concentrations than those of cryptogein. Phytoalexin production was lower in response to both elicitins in N. tabacum var Xanthi cells than in N. rustica cells, and capsicein was the most efficient elicitor of this response. In cryptogein-treated cell suspensions, phytoalexin synthesis was unaffected by diphenyleneiodonium, which inhibited AOS generation, nor was it affected by tiron or catalase, which suppressed AOS accumulation in the extracellular medium. These results suggest that AOS production, lipid peroxidation, and necrosis are directly related, whereas phytoalexin production depends on neither the presence nor the intensity of these responses. PMID:12226334

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  6. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo

    PubMed Central

    Salin, Karine; Auer, Sonya K.; Rudolf, Agata M.; Anderson, Graeme J.; Cairns, Andrew G.; Mullen, William; Hartley, Richard C.; Selman, Colin; Metcalfe, Neil B.

    2015-01-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  7. Photoirradiation of dehydropyrrolizidine alkaloids--formation of reactive oxygen species and induction of lipid peroxidation.

    PubMed

    Zhao, Yuewei; Xia, Qingsu; Yin, Jun Jie; Lin, Ge; Fu, Peter P

    2011-09-10

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated in the presence of superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. Electron spin resonance (ESR) spin trapping studies confirmed that both singlet oxygen and superoxide anion radical were formed during photoirradiation. These results indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation of the parent PAs and other PA metabolites, including PA N-oxides, under similar experimental conditions did not produce lipid peroxidation. It is known that PAs induce skin cancer and are secondary (hepatogenous) photosensitization agents. Our results suggest that dehydro-PAs are the active metabolites responsible for skin cancer formation and PA-induced secondary photosensitization. PMID:21723383

  8. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo.

    PubMed

    Salin, Karine; Auer, Sonya K; Rudolf, Agata M; Anderson, Graeme J; Cairns, Andrew G; Mullen, William; Hartley, Richard C; Selman, Colin; Metcalfe, Neil B

    2015-09-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  9. Mitochondrial Respiration Deficits Driven by Reactive Oxygen Species in Experimental Temporal Lobe Epilepsy

    PubMed Central

    Rowley, Shane; Liang, Li-Ping; Fulton, Ruth; Shimizu, Takahiko; Day, Brian; Patel, Manisha

    2015-01-01

    Metabolic alterations have been implicated in the etiology of temporal lobe epilepsy (TLE), but whether or not they have a functional impact on cellular energy producing pathways (glycolysis and/or oxidative phosphorylation) is unknown. The goal of this study was to determine if alterations in cellular bioenergetics occur using real-time analysis of mitochondrial oxygen consumption and glycolytic rates in an animal model of TLE. We hypothesized that increased steady-state levels of reactive oxygen species (ROS) initiated by epileptogenic injury result in impaired mitochondrial respiration. We established methodology for assessment of bioenergetic parameters in isolated synaptosomes from the hippocampus of Sprague-Dawley rats at various times in the kainate (KA) model of TLE. Deficits in indices of mitochondrial respiration were observed at time points corresponding with the acute and chronic phases of epileptogenesis. We asked if mitochondrial bioenergetic dysfunction occurred as a result of increased mitochondrial ROS and if it could be attenuated in the KA model by pharmacologically scavenging ROS. Increased steady-state ROS in mice with forebrain-specific conditional deletion of manganese superoxide dismutase (Sod2fl/flNEXCre/Cre) in mice resulted in profound deficits in mitochondrial oxygen consumption. Pharmacological scavenging of ROS with a catalytic antioxidant restored mitochondrial respiration deficits in the KA model of TLE. Together, these results demonstrate that mitochondrial respiration deficits occur in experimental TLE and ROS mechanistically contribute to these deficits. Furthermore, this study provides novel methodology for assessing cellular metabolism during the entire time course of disease development. PMID:25600213

  10. Reperfusion injury and reactive oxygen species: The evolution of a concept☆

    PubMed Central

    Granger, D. Neil; Kvietys, Peter R.

    2015-01-01

    Reperfusion injury, the paradoxical tissue response that is manifested by blood flow-deprived and oxygen-starved organs following the restoration of blood flow and tissue oxygenation, has been a focus of basic and clinical research for over 4-decades. While a variety of molecular mechanisms have been proposed to explain this phenomenon, excess production of reactive oxygen species (ROS) continues to receive much attention as a critical factor in the genesis of reperfusion injury. As a consequence, considerable effort has been devoted to identifying the dominant cellular and enzymatic sources of excess ROS production following ischemia-reperfusion (I/R). Of the potential ROS sources described to date, xanthine oxidase, NADPH oxidase (Nox), mitochondria, and uncoupled nitric oxide synthase have gained a status as the most likely contributors to reperfusion-induced oxidative stress and represent priority targets for therapeutic intervention against reperfusion-induced organ dysfunction and tissue damage. Although all four enzymatic sources are present in most tissues and are likely to play some role in reperfusion injury, priority and emphasis has been given to specific ROS sources that are enriched in certain tissues, such as xanthine oxidase in the gastrointestinal tract and mitochondria in the metabolically active heart and brain. The possibility that multiple ROS sources contribute to reperfusion injury in most tissues is supported by evidence demonstrating that redox-signaling enables ROS produced by one enzymatic source (e.g., Nox) to activate and enhance ROS production by a second source (e.g., mitochondria). This review provides a synopsis of the evidence implicating ROS in reperfusion injury, the clinical implications of this phenomenon, and summarizes current understanding of the four most frequently invoked enzymatic sources of ROS production in post-ischemic tissue. PMID:26484802

  11. UVB dependence of quantum dot reactive oxygen species generation in common skin cell models

    PubMed Central

    MORTENSEN, LUKE J.; FAULKNOR, RENEA; RAVICHANDRAN, SUPRIYA; ZHENG, HONG; DELOUISE, LISA A.

    2015-01-01

    Studies have shown that UVB can slightly increase the penetration of nanoparticles through skin and significantly alter skin cell biology, thus it is important to understand if and how UVB may impact subsequent nanoparticle skin cell interactions. The research presented herein evaluates the effect of UVB on quantum dot (QD) uptake and reactive oxygen species (ROS) generation in primary keratinocytes, primary melanocytes, and related cell lines. QD exposure induced cell type dependent ROS responses increased by pre-exposing cells to UVB and correlated with the level of QD uptake. Our results suggest that keratinocytes may be at greater risk for QD induced ROS generation than melanocytes, and raise awareness about the differential cellular effects that topically applied nanomaterials may have on UVB exposed skin. PMID:26485933

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

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy; Syvash, Alexander; Klymchuk, Dmytro

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

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

    NASA Astrophysics Data System (ADS)

    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. Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube Based-Electrocatalytic Intracellular Sensor.

    PubMed

    Rawson, Frankie J; Hicks, Jacqueline; Dodd, Nicholas; Abate, Wondwossen; Garrett, David J; Yip, Nga; Fejer, Gyorgy; Downard, Alison J; Baronian, Kim H R; Jackson, Simon K; Mendes, Paula M

    2015-10-28

    Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular "pulse" of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection. PMID:26438964

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

    PubMed Central

    Halliwell, B; Cross, C E

    1994-01-01

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

  16. Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube Based-Electrocatalytic Intracellular Sensor

    PubMed Central

    2015-01-01

    Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular “pulse” of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection. PMID:26438964

  17. Reactive oxygen species production in single cells following laser irradiation (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Duquette, Michelle L.; Kim, Justine; Shi, Linda Z.; Berns, Michael W.

    2015-08-01

    Region specific DNA breaks can be created in single cells using laser light that damages DNA but does not directly generate reactive oxygen species (ROS). We have examined the cellular response to directly generated DNA breaks in single cells. Using a combination of ROS specific dyes and oxidase inhibitors we have found that the oxidase and chromatin remodeling protein Lysine demethylase I (LSD1) generates detectable ROS as a byproduct of its chromatin remodeling activity during the initial DNA damage response. ROS is produced at detectable amounts primarily within the first 3 minutes post irradiation. LSD1 activity has been previously associated with transcriptional regulation therefore these findings have implications for regulation of gene expression following DNA damage particularly in cells with altered redox states.

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

    PubMed Central

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

    2013-01-01

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

  19. Salicylic acid and reactive oxygen species interplay in the transcriptional control of defense genes expression

    PubMed Central

    Herrera-Vásquez, Ariel; Salinas, Paula; Holuigue, Loreto

    2015-01-01

    It is well established that salicylic acid (SA) plays a critical role in the transcriptional reprograming that occurs during the plant defense response against biotic and abiotic stress. In the course of the defense response, the transcription of different sets of defense genes is controlled in a spatio-temporal manner via SA-mediated mechanisms. Interestingly, different lines of evidence indicate that SA interplays with reactive oxygen species (ROS) and glutathione (GSH) in stressed plants. In this review we focus on the evidence that links SA, ROS, and GSH signals to the transcriptional control of defense genes. We discuss how redox modifications of regulators and co-regulators involved in SA-mediated transcriptional responses control the temporal patterns of gene expression in response to stress. Finally, we examine how these redox sensors are coordinated with the dynamics of cellular redox changes occurring in the defense response to biotic and abiotic stress. PMID:25852720

  20. Salicylic acid and reactive oxygen species interplay in the transcriptional control of defense genes expression.

    PubMed

    Herrera-Vásquez, Ariel; Salinas, Paula; Holuigue, Loreto

    2015-01-01

    It is well established that salicylic acid (SA) plays a critical role in the transcriptional reprograming that occurs during the plant defense response against biotic and abiotic stress. In the course of the defense response, the transcription of different sets of defense genes is controlled in a spatio-temporal manner via SA-mediated mechanisms. Interestingly, different lines of evidence indicate that SA interplays with reactive oxygen species (ROS) and glutathione (GSH) in stressed plants. In this review we focus on the evidence that links SA, ROS, and GSH signals to the transcriptional control of defense genes. We discuss how redox modifications of regulators and co-regulators involved in SA-mediated transcriptional responses control the temporal patterns of gene expression in response to stress. Finally, we examine how these redox sensors are coordinated with the dynamics of cellular redox changes occurring in the defense response to biotic and abiotic stress. PMID:25852720

  1. Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis

    PubMed Central

    Liu, Rui-Ming; Desai, Leena P.

    2015-01-01

    Transforming growth factor beta (TGF-β) is the most potent pro-fibrogenic cytokine and its expression is increased in almost all of fibrotic diseases. Although signaling through Smad pathway is believed to play a central role in TGF-β's fibrogenesis, emerging evidence indicates that reactive oxygen species (ROS) modulate TGF-β's signaling through different pathways including Smad pathway. TGF-β1 increases ROS production and suppresses antioxidant enzymes, leading to a redox imbalance. ROS, in turn, induce/activate TGF-β1 and mediate many of TGF-β's fibrogenic effects, forming a vicious cycle (see graphic flow chart on the right). Here, we review the current knowledge on the feed-forward mechanisms between TGF-β1 and ROS in the development of fibrosis. Therapeutics targeting TGF-β-induced and ROS-dependent cellular signaling represents a novel approach in the treatment of fibrotic disorders. PMID:26496488

  2. Regulation of plant reactive oxygen species (ROS) in stress responses: learning from AtRBOHD.

    PubMed

    Liu, Yukun; He, Chengzhong

    2016-05-01

    Reactive oxygen species (ROS) are constantly produced in plants, as the metabolic by-products or as the signaling components in stress responses. High levels of ROS are harmful to plants. In contrast, ROS play important roles in plant physiology, including abiotic and biotic tolerance, development, and cellular signaling. Therefore, ROS production needs to be tightly regulated to balance their function. Respiratory burst oxidase homologue (RBOH) proteins, also known as plant nicotinamide adenine dinucleotide phosphate oxidases, are well studied enzymatic ROS-generating systems in plants. The regulatory mechanisms of RBOH-dependent ROS production in stress responses have been intensively studied. This has greatly advanced our knowledge of the mechanisms that regulate plant ROS production. This review attempts to integrate the regulatory mechanisms of RBOHD-dependent ROS production by discussing the recent advance. AtRBOHD-dependent ROS production could provide a valuable reference for studying ROS production in plant stress responses. PMID:26883222

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

    PubMed

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

    2011-08-01

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

  4. Signaling Networks Involving Reactive Oxygen Species and Ca2+ in Plants

    NASA Astrophysics Data System (ADS)

    Kuchitsu, Kazuyuki

    2013-01-01

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

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

    SciTech Connect

    Puranam, Kasturi L.; Wu, Guanghong; Strittmatter, Warren J.; Burke, James R. . E-mail: james.burke@duke.edu

    2006-03-10

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

  6. Evidence for photochemical production of reactive oxygen species in desert soils.

    PubMed

    Georgiou, Christos D; Sun, Henry J; McKay, Christopher P; Grintzalis, Konstantinos; Papapostolou, Ioannis; Zisimopoulos, Dimitrios; Panagiotidis, Konstantinos; Zhang, Gaosen; Koutsopoulou, Eleni; Christidis, George E; Margiolaki, Irene

    2015-01-01

    The combination of intense solar radiation and soil desiccation creates a short circuit in the biogeochemical carbon cycle, where soils release significant amounts of CO2 and reactive nitrogen oxides by abiotic oxidation. Here we show that desert soils accumulate metal superoxides and peroxides at higher levels than non-desert soils. We also show the photogeneration of equimolar superoxide and hydroxyl radical in desiccated and aqueous soils, respectively, by a photo-induced electron transfer mechanism supported by their mineralogical composition. Reactivity of desert soils is further supported by the generation of hydroxyl radical via aqueous extracts in the dark. Our findings extend to desert soils the photogeneration of reactive oxygen species by certain mineral oxides and also explain previous studies on desert soil organic oxidant chemistry and microbiology. Similar processes driven by ultraviolet radiation may be operating in the surface soils on Mars. PMID:25960012

  7. Mitochondria and reactive oxygen and nitrogen species in neurological disorders and stroke: Therapeutic implications.

    PubMed

    Bolaños, Juan P; Moro, Maria A; Lizasoain, Ignacio; Almeida, Angeles

    2009-11-30

    Mitochondria represent both the main source and target of reactive oxygen and nitrogen species (RONS). In view of the large energy expenditure made by neurons during neurotransmission, an intact mitochondrial function is of paramount importance for the correct function of the brain. Accordingly, the search of therapeutic strategies against situations in which there is an abnormal brain function, such as neurological disorders and stroke, should be focused towards mitochondria. Here, we have reviewed the normal and abnormal mitochondrial bioenergetics and dynamics, highlighting the relevance that, for these processes in the brain RONS exert. Evidence suggests that disruption of mitochondrial bioenergetics and dynamics may have a critical role in the pathogenesis of these brain diseases. Drug therapies directed toward providing safer mitochondria are currently under both pre- and clinical investigations. PMID:19716390

  8. PGC-1α and Reactive Oxygen Species Regulate Human Embryonic Stem Cell-Derived Cardiomyocyte Function

    PubMed Central

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

    2013-01-01

    Summary Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during development of cardiomyocytes, decreased mitochondrial content and activity and decreased the capacity for coping with energetic stress. Yet, concurrently, reactive oxygen species (ROS) levels were lowered, and the amplitude of the action potential and the maximum amplitude of the calcium transient were in fact increased. Importantly, in control cardiomyocytes, lowering ROS levels emulated this beneficial effect of PGC-1α knockdown and similarly increased the calcium transient amplitude. Our results suggest that controlling ROS levels may be of key physiological importance for recapitulating mature cardiomyocyte phenotypes, and the combination of bioassays used in this study may have broad application in the analysis of cardiac physiology pertaining to disease. PMID:24371810

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

    Halliwell, B. |; Cross, C.E.

    1994-12-01

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

  11. Reactive oxygen species production and antioxidant enzyme activity during epididymal sperm maturation in Corynorhinus mexicanus bats.

    PubMed

    Edith, Arenas-Ríos; Adolfo, Rosado García; Edith, Cortés-Barberena; Mina, Königsberg; Marcela, Arteaga-Silva; Ahiezer, Rodríguez-Tobón; Gisela, Fuentes-Mascorro; Angel, León-Galván Miguel

    2016-03-01

    Prolonged sperm storage in the epididymis of Corynorhinus mexicanus bats after testicular regression has been associated with epididymal sperm maturation in the caudal region, although the precise factors linked with this phenomenon are unknown. The aim of this work is to determine the role of reactive oxygen species (ROS) and changes in antioxidant enzymatic activity occurring in the spermatozoa and epididymal fluid over time, in sperm maturation and storage in the caput, corpus and cauda of the bat epididymis. Our data showed that an increment in ROS production coincided with an increase in superoxide dismutase (SOD) activity in epididymal fluid and with a decrease in glutathione peroxidase (GPX) activity in the spermatozoa in at different time points and epididymal regions. The increase in ROS production was not associated with oxidative damage measured by lipid peroxidation. The results of the current study suggest the existence of a shift in the redox balance, which might be associated with sperm maturation and storage. PMID:26952757

  12. Mechanisms that Regulate Production of Reactive Oxygen Species by Cytochrome P450

    SciTech Connect

    Zangar, Richard C.; Davydov, Dmitri R.; Verma, Seema

    2004-09-15

    Mammalian cytochromes P450 (P450) are a family of heme-thiolate enzymes involved in the oxidative metabolism of a variety of endogenous and exogenous lipophilic compounds. Poor coupling of the P450 catalytic cycle results in continuous production of reactive oxygen species (ROS), which affect signaling pathways and other cellular functions. P450 generation of ROS is tightly controlled by regulation of gene transcription, as well as by modulation of interactions between protein constituents of the monooxygenase that affects its activity, coupling and stability. Malfunction of these mechanisms may result in a burst of ROS production, which can cause lipid peroxidation and oxidative stress. In turn, oxidative stress downregulates P450 levels by a variety of feedback mechanisms. This review provides an overview of recent advances in our understanding of these feedback mechanisms that serve to limit P450 production of ROS. Some of the more likely physiological and cellular effects of P450 generation of ROS are also discussed.

  13. Role of Reactive Oxygen Species in Pathogenesis of Radiocontrast-Induced Nephropathy

    PubMed Central

    Pisani, Antonio; Faga, Teresa; Ashour, Michael; Di Nuzzi, Antonella; Mancini, Aldo

    2013-01-01

    In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of reactive oxygen species (ROS) in the kidney following the administration of iodinated contrast media, which play a relevant role in the development of contrast media-induced nephropathy. Many studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetylcysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging. PMID:24459673

  14. Zinc Induces Apoptosis of Human Melanoma Cells, Increasing Reactive Oxygen Species, p53 and FAS Ligand.

    PubMed

    Provinciali, Mauro; Pierpaoli, Elisa; Bartozzi, Beatrice; Bernardini, Giovanni

    2015-10-01

    The aim of this study was to examine the in vitro effect of zinc on the apoptosis of human melanoma cells, by studying the zinc-dependent modulation of intracellular levels of reactive oxygen species (ROS) and of p53 and FAS ligand proteins. We showed that zinc concentrations ranging from 33.7 μM to 75 μM Zn(2+) induced apoptosis in the human melanoma cell line WM 266-4. This apoptosis was associated with an increased production of intracellular ROS, and of p53 and FAS ligand protein. Treatment of tumor cells with the antioxidant N-acetylcysteine was able to prevent Zn(2+)-induced apoptosis, as well as the increase of p53 and FAS ligand protein induced by zinc. Zinc induces apoptosis in melanoma cells by increasing ROS and this effect may be mediated by the ROS-dependent induction of p53 and FAS/FAS ligand. PMID:26408691

  15. High osmotic pressure increases reactive oxygen species generation in rabbit corneal epithelial cells by endoplasmic reticulum

    PubMed Central

    Wang, Peng; Sheng, Minjie; Li, Bing; Jiang, Yaping; Chen, Yihui

    2016-01-01

    Tear high osmotic pressure (HOP) has been recognized as the core mechanism underlying ocular surface inflammation, injury and symptoms and is closely associated with many ocular surface diseases, especially dry eye. The endoplasmic reticulum (ER) is a multi-functional organelle responsible for protein synthesis, folding and transport, biological synthesis of lipids, vesicle transport and intracellular calcium storage. Accumulation of unfolded proteins and imbalance of calcium ion in the ER would induce ER stress and protective unfolded protein response (UPR). Many studies have demonstrated that ER stress can induce cell apoptosis. However, the association between tear HOP and ER stress has not been studied systematically. In the present study, rabbit corneal epithelial cells were treated with HOP and results showed that the production of reactive oxygen species increased markedly, which further activated the ER signaling pathway and ultimately induced cell apoptosis. These findings shed new lights on the pathogenesis and clinical treatment of dry eye and other ocular surface diseases. PMID:27158374

  16. Respiratory protein-generated reactive oxygen species as an antimicrobial strategy.

    PubMed

    Jiang, Naxin; Tan, Nguan Soon; Ho, Bow; Ding, Jeak Ling

    2007-10-01

    The evolution of the host-pathogen relationship comprises a series of invasive-defensive tactics elicited by both participants. The stereotype is that the antimicrobial immune response requires multistep processes. Little is known about the primordial immunosurveillance system, which probably has components that directly link sensors and effectors. Here we found that the respiratory proteins of both the horseshoe crab and human were directly activated by microbial proteases and were enhanced by pathogen-associated molecular patterns, resulting in the production of more reactive oxygen species. Hemolytic virulent pathogens, which produce proteases as invasive factors, are more susceptible to this killing mechanism. This 'shortcut' antimicrobial strategy represents a fundamental and universal mode of immunosurveillance, which has been in existence since before the split of protostomes and deuterostomes and still persists today. PMID:17721536

  17. Electrocatalytic performances of N-doped graphene with anchored iridium species in oxygen reduction reaction

    NASA Astrophysics Data System (ADS)

    Choi, Kwangrok; Lee, Seungjun; Shim, Yeonjun; Oh, Junghoon; Kim, Sujin; Park, Sungjin

    2015-09-01

    Development of new systems with high catalytic performances in the oxygen reduction reaction (ORR) for practical applications in fuel cells and metal-air batteries is a challenge. We develop a one-pot solution method for producing a novel hybrid material consisting of Ir species anchored on N-doped graphene. The hybrid is synthesized by reacting graphene oxide with IrCl3 · xH2O in dimethylformamide under reflux. Chemical and structural analyses confirm the attachment of Ir atoms to the N and O atoms of the N-doped graphene-based materials. The hybrid shows a good electrocatalytic performance for the ORR in alkaline media, with an onset potential of 0.88 V (versus the reversible hydrogen electrode), high long-term durability, and good tolerance for methanol poisoning.

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

    PubMed Central

    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

  19. Mold elicits atopic dermatitis by reactive oxygen species: Epidemiology and mechanism studies.

    PubMed

    Kim, Ha-Jung; Lee, Eun; Lee, Seung-Hwa; Kang, Mi-Jin; Hong, Soo-Jong

    2015-12-01

    Mold has been implicated in the development of atopic dermatitis (AD); however, the underlying mechanisms remain unknown. The aim of the study was to investigate the effects of mold exposure in early life through epidemiologic and mechanistic studies in vivo and in vitro. Exposure to visible mold inside the home during the first year of life was associated with an increased risk for current AD by two population-based cross-sectional human studies. Children with the AG+GG genotype of GSTP1 showed increased risk for current AD when exposed to mold. In the mouse model, treatment with patulin induced and aggravated clinically significant AD and Th2-related inflammation of the affected mouse skin. Additionally, reactive oxygen species (ROS) were released in the mouse skin as well by human keratinocytes. In conclusions, mold exposure increases the risk for AD related to ROS generation mediated by Th2-promoting inflammatory cytokines. PMID:26205459

  20. Reactive oxygen species generated from skeletal muscles are required for gecko tail regeneration

    PubMed Central

    Zhang, Qing; Wang, Yingjie; Man, Lili; Zhu, Ziwen; Bai, Xue; Wei, Sumei; Liu, Yan; Liu, Mei; Wang, Xiaochuan; Gu, Xiaosong; Wang, Yongjun

    2016-01-01

    Reactive oxygen species (ROS) participate in various physiological and pathological functions following generation from different types of cells. Here we explore ROS functions on spontaneous tail regeneration using gecko model. ROS were mainly produced in the skeletal muscle after tail amputation, showing a temporal increase as the regeneration proceeded. Inhibition of the ROS production influenced the formation of autophagy in the skeletal muscles, and as a consequence, the length of the regenerating tail. Transcriptome analysis has shown that NADPH oxidase (NOX2) and the subunits (p40phox and p47phox) are involved in the ROS production. ROS promoted the formation of autophagy through regulation of both ULK and MAPK activities. Our results suggest that ROS produced by skeletal muscles are required for the successful gecko tail regeneration. PMID:26853930

  1. Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer's disease: the NF-κB connection.

    PubMed

    Kaur, Upinder; Banerjee, Priyanjalee; Bir, Aritri; Sinha, Maitrayee; Biswas, Atanu; Chakrabarti, Sasanka

    2015-01-01

    Oxidative stress and inflammatory response are important elements of Alzheimer's disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-κB and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD. The possibility of identifying new disease-modifying drugs for AD targeting NF-κBsignaling cascade has been discussed in the end. PMID:25620241

  2. Propofol scavenges reactive oxygen species and inhibits the protein nitration induced by activated polymorphonuclear neutrophils.

    TOXLINE Toxicology Bibliographic Information

    Thiry JC; Hans P; Deby-Dupont G; Mouythis-Mickalad A; Bonhomme V; Lamy M

    2004-09-19

    Activated polymorphonuclear neutrophils may damage tissues through the release of biochemical mediators. Among them, peroxynitrite is responsible for hydroxylation reactions and nitration of proteins, or is metabolised into nitrate. We investigated the effect of propofol on the production of reactive oxygen species, the nitration of proteins and the formation of nitrate by activated human polymorphonuclear neutrophils. Propofol dose-dependently inhibited chemiluminescence, nitration of proteins and nitrate production in a concentration range from 10(-3) to 10(-6) mM. A significant correlation was observed between the logarithm of propofol concentration and the intensity of chemiluminescence (r2=0.90), the nitration of proteins (r2=0.67) and the production of nitrate (r2=0.79). Those results are consistent with the scavenging effect of propofol on peroxynitrite and could confer a protective property to propofol in pathological situations involving polymorphonuclear neutrophils activation.

  3. Propofol scavenges reactive oxygen species and inhibits the protein nitration induced by activated polymorphonuclear neutrophils.

    PubMed

    Thiry, Jean-Christophe; Hans, Pol; Deby-Dupont, Ginette; Mouythis-Mickalad, Ange; Bonhomme, Vincent; Lamy, Maurice

    2004-09-19

    Activated polymorphonuclear neutrophils may damage tissues through the release of biochemical mediators. Among them, peroxynitrite is responsible for hydroxylation reactions and nitration of proteins, or is metabolised into nitrate. We investigated the effect of propofol on the production of reactive oxygen species, the nitration of proteins and the formation of nitrate by activated human polymorphonuclear neutrophils. Propofol dose-dependently inhibited chemiluminescence, nitration of proteins and nitrate production in a concentration range from 10(-3) to 10(-6) mM. A significant correlation was observed between the logarithm of propofol concentration and the intensity of chemiluminescence (r2=0.90), the nitration of proteins (r2=0.67) and the production of nitrate (r2=0.79). Those results are consistent with the scavenging effect of propofol on peroxynitrite and could confer a protective property to propofol in pathological situations involving polymorphonuclear neutrophils activation. PMID:15363948

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

    PubMed Central

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

    2013-01-01

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

  5. Juglone induces cell death of Acanthamoeba through increased production of reactive oxygen species.

    PubMed

    Jha, Bijay Kumar; Jung, Hui-Jung; Seo, Incheol; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki

    2015-12-01

    Juglone (5-hydroxy-1,4-naphthoquinone) is a major chemical constituent of Juglans mandshruica Maxim. Recent studies have demonstrated that juglone exhibits anti-cancer, anti-bacterial, anti-viral, and anti-parasitic properties. However, its effect against Acanthamoeba has not been defined yet. The aim of this study was to investigate the effect of juglone on Acanthamoeba. We demonstrate that juglone significantly inhibits the growth of Acanthamoeba castellanii at 3-5 μM concentrations. Juglone increased the production of reactive oxygen species (ROS) and caused cell death of A. castellanii. Inhibition of ROS by antioxidant N-acetyl-l-cysteine (NAC) restored the cell viability. Furthermore, our results show that juglone increased the uptake of mitochondrial specific dye. Collectively, these results indicate that ROS played a significant role in the juglone-induced cell death of Acanthamoeba. PMID:26358271

  6. Curcumin mitigates the fibrillation of human serum albumin and diminishes the formation of reactive oxygen species.

    PubMed

    Mazaheri, Mansooreh; Moosavi-Movahedi, Ali Akbar; Saboury, Ali Akbar; Rezaei, Mehran Habibi; Shourian, Mostafa; Farhadi, Mohammad; Sheibani, Nader

    2015-01-01

    The formation of amyloid fibrils are thought to contribute to pathogenesis of many amyloids associated human diseases. Here the impact of curcumin on amyloid formation of human serum albumin (HSA) was studied. Incubation of HSA at 68°C under physiologic pH led to amyloid fibril formation. Thioflavin T (ThT) fluorescence was used for determination of amyloid fibril formation. Atomic force microscopy experiments indicated different fibril structure of HSA incubated with or without curcumin. The monitoring of the changes in reactive oxygen species (ROS) levels upon incubation of curcumin with HSA showed a significant decrease in ROS levels. Similar experiments were also carried out in the presence of aflatoxin M1 (AFM1) and lead (Pb) ions. Our results indicated that AFM1 and Pb ions promote the fibrillation of HSA and accelerate ROS production, which were inhibited in the presence of curcumin. Thus, curcumin mitigates protein fibrillation activity and diminishes ROS generation. PMID:25666039

  7. The Role of Mitochondria in Reactive Oxygen Species Metabolism and Signaling

    PubMed Central

    Starkov, Anatoly A.

    2010-01-01

    Oxidative stress is considered a major contributor to the etiology of both “normal” senescence and severe pathologies with serious public health implications. Several cellular sources, including mitochondria, are known to produce significant amounts of reactive oxygen species (ROS) that may contribute to intracellular oxidative stress. Mitochondria possess at least 10 known sites that are capable of generating ROS, but they also feature a sophisticated multilayered ROS defense system that is much less studied. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal at the level of mitochondria. An integrative systemic approach is applied to analysis of mitochondrial ROS metabolism, which is “dissected” into ROS generation, ROS emission, and ROS scavenging. The in vitro ROS-producing capacity of several mitochondrial sites is compared in the metabolic context and the role of mitochondria in ROS-dependent intracellular signaling is discussed. PMID:19076429

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    Sun, Qingrui; Chen, Tongsheng

    2009-02-01

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

  10. High fluence laser irradiation induces reactive oxygen species generation in human lung adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Wang, Fang; Xing, Da; Chen, Tong-Sheng

    2006-09-01

    Low-power laser irradiation (LPLI) has been used for therapies such as curing spinal cord injury, healing wound et al. Yet, the mechanism of LPLI remains unclear. Our previous study showed that low fluences laser irradiation induces human lung adenocarcinoma cells (ASTC-a-1) proliferation, but high fluences induced apoptosis and caspase-3 activation. In order to study the mechanism of apoptosis induced by high fluences LPLI further, we have measured the dynamics of generation of reactive oxygen species (ROS) using H IIDCFDA fluorescence probes during this process. ASTC-a-1 cells apoptosis was induced by He-Ne laser irradiation at high fluence of 120J/cm2. A confocal laser scanning microscope was used to perform fluorescence imaging. The results demonstrated that high fluence LPLI induced the increase of mitochondria ROS. Our studies contribute to clarify the biological mechanism of high fluence LPLI-induced cell apoptosis.

  11. Feline mesenchymal stem cells and supernatant inhibit reactive oxygen species production in cultured feline neutrophils.

    PubMed

    Mumaw, Jennifer L; Schmiedt, Chad W; Breidling, Sarah; Sigmund, Alex; Norton, Natalie A; Thoreson, Merrilee; Peroni, John F; Hurley, David J

    2015-12-01

    Feline bone marrow-derived MSCs (BMMSCs), adipose-derived MSCs (AMSCs) and fibroblasts (FBs) were isolated and cultured. Tri-lineage differentiation assays and flow cytometry were used to characterize MSCs. Neutrophils (NPs) were isolated from whole blood and the NPs production of reactive oxygen reactive oxygen species (ROS) was measured. NPs were cultured alone, with MSC culture supernatant (SN), BMMSCs or AMSCs. NPs incubated with BMMSCs had significantly lower ROS production than NPs incubated with AMSCs (p=0.0006) or FB (p<0.0001); NPs ROS production significantly decreased with increasing BMMSC cell number (p=0.0023) and significantly increased with NPs were incubated with FB compared to BMMSC (p=0.0003). Both BMMSC SN and AMSC SN had statistically significantly lower ROS production than FB SN when incubated with NPs (both p<0.0001). ROS production was significantly reduced with increased fractions of SN from BMMSCs (p=0.0467) and AMSCs (p=0.0017). PMID:26679797

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

    PubMed

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

    2002-05-31

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

  13. Development of micellar reactive oxygen species assay for photosafety evaluation of poorly water-soluble chemicals.

    PubMed

    Seto, Yoshiki; Kato, Masashi; Yamada, Shizuo; Onoue, Satomi

    2013-09-01

    A reactive oxygen species (ROS) assay was previously developed for photosafety assessment; however, the phototoxic potential of some chemicals cannot be evaluated because of their limited aqueous solubility. The present study was undertaken to develop a new micellar ROS (mROS) assay system for poorly water-soluble chemicals using a micellar solution of 0.5% (v/v) Tween 20 for solubility enhancement. In repeated mROS assay, intra- and inter-day precisions (coefficient of variation) were found to be below 11%, and the Z'-factors for singlet oxygen and superoxide suggested a large separation band between positive and negative standards. The ROS and mROS assays were applied to 65 phototoxins and 18 non-phototoxic compounds for comparative purposes. Of all 83 chemicals, 25 were unevaluable in the ROS assay due to poor solubility, but only 2 were in the mROS assay. Upon mROS assay on these model chemicals, the individual specificity was 76.5%, and the positive and negative predictivities were found to be 93.9% and 86.7%, respectively. The mROS assay provided 2 false negative predictions, although negative predictivity for the ROS assay was found to be 100%. Considering the pros and cons of these assays, strategic combined use of the ROS and mROS assays might be efficacious for reliable photosafety assessment with high applicability and predictivity. PMID:23727251

  14. Mutagenicity induced by UVC in Escherichia coli cells: reactive oxygen species involvement.

    PubMed

    Silva-Júnior, A C T; Asad, L M B O; Felzenszwalb, I; Asad, N R

    2011-01-01

    We previously demonstrated that reactive oxygen species (ROS) could be involved in the DNA damage induced by ultraviolet-C (UVC). In this study, we evaluated singlet oxygen ((1)O(2)) involvement in UVC-induced mutagenesis in Escherichia coli cells. First, we found that treatment with sodium azide, an (1)O(2) chelator, protected cells against UVC-induced lethality. The survival assay showed that the fpg mutant was more resistant to UVC lethality than the wild-type strain. The rifampicin mutagenesis assay showed that UVC mutagenesis was inhibited five times more in cells treated with sodium azide, and stimulated 20% more fpg mutant. These results suggest that (1)O(2) plays a predominant role in UVC-induced mutagenesis. (1)O(2) generates a specific mutagenic lesion, 8-oxoG, which is repaired by Fpg protein. This lesion was measured by GC-TA reversion in the CC104 strain, its fpg mutant (BH540), and both CC104 and BH540 transformed with the plasmid pFPG (overexpression of Fpg protein). This assay showed that mutagenesis was induced 2.5-fold in the GC-TA strain and 7-fold in the fpg mutant, while the fpg mutant transformed with pFPG was similar to GC-TA strain. This suggests that UVC can also cause ROS-mediated mutagenesis and that the Fpg protein may be involved in this repair. PMID:22005338

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

    PubMed Central

    Matsubara, Keiichi; Higaki, Takashi; Matsubara, Yuko; Nawa, Akihiro

    2015-01-01

    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. PMID:25739077

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

    PubMed

    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. PMID:19483186

  17. Reactive oxygen species as universal constraints in life-history evolution

    PubMed Central

    Dowling, Damian K.; Simmons, Leigh W.

    2009-01-01

    Evolutionary theory is firmly grounded on the existence of trade-offs between life-history traits, and recent interest has centred on the physiological mechanisms underlying such trade-offs. Several branches of evolutionary biology, particularly those focusing on ageing, immunological and sexual selection theory, have implicated reactive oxygen species (ROS) as profound evolutionary players. ROS are a highly reactive group of oxygen-containing molecules, generated as common by-products of vital oxidative enzyme complexes. Both animals and plants appear to intentionally harness ROS for use as molecular messengers to fulfil a wide range of essential biological processes. However, at high levels, ROS are known to exert very damaging effects through oxidative stress. For these reasons, ROS have been suggested to be important mediators of the cost of reproduction, and of trade-offs between metabolic rate and lifespan, and between immunity, sexual ornamentation and sperm quality. In this review, we integrate the above suggestions into one life-history framework, and review the evidence in support of the contention that ROS production will constitute a primary and universal constraint in life-history evolution. PMID:19324792

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

    PubMed

    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. PMID:24771559

  19. Bistability of Mitochondrial Respiration Underlies Paradoxical Reactive Oxygen Species Generation Induced by Anoxia

    PubMed Central

    Selivanov, Vitaly A.; Votyakova, Tatyana V.; Zeak, Jennifer A.; Trucco, Massimo; Roca, Josep; Cascante, Marta

    2009-01-01

    Increased production of reactive oxygen species (ROS) in mitochondria underlies major systemic diseases, and this clinical problem stimulates a great scientific interest in the mechanism of ROS generation. However, the mechanism of hypoxia-induced change in ROS production is not fully understood. To mathematically analyze this mechanism in details, taking into consideration all the possible redox states formed in the process of electron transport, even for respiratory complex III, a system of hundreds of differential equations must be constructed. Aimed to facilitate such tasks, we developed a new methodology of modeling, which resides in the automated construction of large sets of differential equations. The detailed modeling of electron transport in mitochondria allowed for the identification of two steady state modes of operation (bistability) of respiratory complex III at the same microenvironmental conditions. Various perturbations could induce the transition of respiratory chain from one steady state to another. While normally complex III is in a low ROS producing mode, temporal anoxia could switch it to a high ROS producing state, which persists after the return to normal oxygen supply. This prediction, which we qualitatively validated experimentally, explains the mechanism of anoxia-induced cell damage. Recognition of bistability of complex III operation may enable novel therapeutic strategies for oxidative stress and our method of modeling could be widely used in systems biology studies. PMID:20041200

  20. Reactive oxygen species inhibit the succinate oxidation-supported generation of membrane potential in wheat mitochondria.

    PubMed

    Pastore, Donato; Laus, Maura Nicoletta; Di Fonzo, Natale; Passarella, Salvatore

    2002-04-10

    In order to gain a first insight into the effects of reactive oxygen species (ROS) on plant mitochondria, we studied the effect of the ROS producing system consisting of xanthine plus xanthine oxidase on the rate of membrane potential (DeltaPsi) generation due to either succinate or NADH addition to durum wheat mitochondria as monitored by safranin fluorescence. We show that the early ROS production inhibits the succinate-dependent, but not the NADH-dependent, DeltaPsi generation and oxygen uptake. This inhibition appears to depend on the impairment of mitochondrial permeability to succinate. It does not involve mitochondrial thiol groups sensitive to either mersalyl or N-ethylmaleimide and might involve both protein residues and/or membrane lipids, as suggested by the mixed nature. We propose that, during oxidative stress, early generation of ROS can affect plant mitochondria by impairing metabolite transport, thus preventing further substrate oxidation, DeltaPsi generation and consequent large-scale ROS production. PMID:11959094

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

    PubMed Central

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

    2014-01-01

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

  2. Transgenic tobacco expressing a foreign calmodulin gene shows an enhanced production of active oxygen species.

    PubMed Central

    Harding, S A; Oh, S H; Roberts, D M

    1997-01-01

    A strategy for elucidating specific molecular targets of calcium and calmodulin in plant defense responses has been developed. We have used a dominant-acting calmodulin mutant (VU-3, Lys to Arg115) to investigate the oxidative burst and nicotinamide co-enzyme fluxes after various stimuli (cellulase, harpin, incompatible bacteria, osmotic and mechanical) that elicit plant defense responses in transgenic tobacco cell cultures. VU-3 calmodulin differs from endogenous plant calmodulin in that it cannot be methylated post-translationally, and as a result it hyperactivates calmodulin-dependent NAD kinase. Cells expressing VU-3 calmodulin exhibited a stronger active oxygen burst that occurred more rapidly than in normal control cells challenged with the same stimuli. Increases in NADPH level were also greater in VU-3 cells and coincided both in timing and magnitude with development of the active oxygen species (AOS) burst. These data show that calmodulin is a target of calcium fluxes in response to elicitor or environmental stress, and provide the first evidence that plant NAD kinase may be a downstream target which potentiates AOS production by altering NAD(H)/NADP(H) homeostasis. PMID:9135130

  3. [Detection of intracellular reactive oxygen species by flow cytometry in Pichia pastoris fermentation].

    PubMed

    Xiao, An-Feng; Zhou, Xiang-Shan; Zhou, Li; Zhang, Yuan-Xing

    2006-03-01

    In Pichia pastoris fermentation, methanol was oxidized into carbon oxide and produced a byproduct H2 O2, one of the partially reduced forms of molecular oxygen known as reactive oxygen species (ROS) . ROS are highly damaging towards cellular constituents. Flow cytometry (FCM) is an excellent method that permits the rapid, optical analysis of individual cells and has many advantages over conventional cytometry. However, its use in detecting intracellular ROS levels during Pichia fermentation was rarely reported. In our work, by means of flow cytometry, two fluorescent dye 2', 7'-dichlorofluorescin diacetate (DCFH-DA) and propidium iodide (PI) were used to detect ROS. The effect of intracellular ROS on Pichia pastoris cells during fermentation was studied through the comparison between DCFH-DA/PI double-stained cells and PI single-stained cells. In this study, the loss of cell viability during fermentation was correlated with the accumulation of ROS. At the glycerol batch and fed-batch phase, little ROS was accumulated intracellularly and cell viability reached almost 100%. At the early methanol fed-batch phase, intracellular ROS accumulation took place but 98.5% cells still kept viable. At the later methanol fed-batch phase, 94.0% cells accumulated high ROS. As a result, some cells lost their viability because of the damage of ROS. 25.4% dead cells accumulated high ROS in the total 29.1% dead cells. PMID:16607956

  4. Association of Reactive Oxygen Species Levels and Radioresistance in Cancer Stem Cells

    PubMed Central

    Diehn, Maximilian; Cho, Robert W.; Lobo, Neethan A.; Kalisky, Tomer; Dorie, Mary Jo; Kulp, Angela N.; Qian, Dalong; Lam, Jessica S.; Ailles, Laurie E.; Wong, Manzhi; Joshua, Benzion; Kaplan, Michael J.; Wapnir, Irene; Dirbas, Fred; Somlo, George; Garberoglio, Carlos; Paz, Benjamin; Shen, Jeannie; Lau, Sean K.; Quake, Stephen R.; Brown, J. Martin; Weissman, Irving L.; Clarke, Michael F.

    2009-01-01

    Metabolism of oxygen, while central to life, also produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease, and aging. It has recently been shown that central nervous system stem cells1, 2 and hematopoietic stem cells and early progenitors3-6 contain lower levels of ROS than their more mature progeny and that these differences appear to be critical for maintaining stem cell function. We hypothesized that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Congruently, subsets of CSCs in some human and murine breast tumors contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing radiation-induced cell killing7, 8, CSCs in these tumors develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacologic depletion of ROS scavengers in CSCs significantly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumors contain lower ROS levels and enhanced ROS defenses compared to their non-tumorigenic progeny, which may contribute to tumor radioresistance. PMID:19194462

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

    PubMed

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

    2009-03-01

    Silver ions have been widely used as disinfectants that inhibit bacterial growth by inhibiting the essential enzymatic functions of the microorganism via interaction with the thiol-group of l-cysteine. However, silver-ion-mediated perturbation of the bacterial respiratory chain has raised the possibility of reactive oxygen species (ROS) generation. We used bacterial reporter strains specifically responding to superoxide radicals and found that silver-ion-mediated ROS-generation affected bactericidal activity. Almost half the log reduction in Escherichia coli and Staphylococcus aureus populations (model strains for gram negative and positive bacteria, respectively) caused by silver-ion disinfection was attributed to ROS-mediated bactericidal activity. The major form of ROS generated was the superoxide-radical; H(2)O(2) was not induced. Furthermore, silver ions strongly enhanced paraquat-induced oxidative stress, indicating close correlation and synergism between the conventional and ROS-mediated silver toxicity. Our results suggest that further studies in silver-based disinfection systems should consider the oxygen concentration and ROS reaction. PMID:19073336

  6. Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy.

    PubMed

    Pearson, Jennifer N; Rowley, Shane; Liang, Li-Ping; White, Andrew M; Day, Brian J; Patel, Manisha

    2015-10-01

    Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it. PMID:26184893

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

    PubMed

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

    2012-06-01

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

  8. Hypoxia-Dependent Reactive Oxygen Species Signaling in the Pulmonary Circulation: Focus on Ion Channels

    PubMed Central

    Veit, Florian; Pak, Oleg; Brandes, Ralf P.

    2015-01-01

    Abstract Significance: An acute lack of oxygen in the lung causes hypoxic pulmonary vasoconstriction, which optimizes gas exchange. In contrast, chronic hypoxia triggers a pathological vascular remodeling causing pulmonary hypertension, and ischemia can cause vascular damage culminating in lung edema. Recent Advances: Regulation of ion channel expression and gating by cellular redox state is a widely accepted mechanism; however, it remains a matter of debate whether an increase or a decrease in reactive oxygen species (ROS) occurs under hypoxic conditions. Ion channel redox regulation has been described in detail for some ion channels, such as Kv channels or TRPC6. However, in general, information on ion channel redox regulation remains scant. Critical Issues and Future Directions: In addition to the debate of increased versus decreased ROS production during hypoxia, we aim here at describing and deciphering why different oxidants, under different conditions, can cause both activation and inhibition of channel activity. While the upstream pathways affecting channel gating are often well described, we need a better understanding of redox protein modifications to be able to determine the complexity of ion channel redox regulation. Against this background, we summarize the current knowledge on hypoxia-induced ROS-mediated ion channel signaling in the pulmonary circulation. Antioxid. Redox Signal. 22, 537–552 PMID:25545236

  9. Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

    PubMed Central

    Klann, Eric

    2011-01-01

    Abstract The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age- or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function. Antioxid. Redox Signal. 14, 2013–2054. PMID:20649473

  10. Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

    PubMed Central

    Wilhelm, Jiří; Vytášek, Richard; Uhlík, Jiří; Vajner, Luděk

    2016-01-01

    Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS. PMID:27190574

  11. Prussian Blue Nanoparticles as Multienzyme Mimetics and Reactive Oxygen Species Scavengers.

    PubMed

    Zhang, Wei; Hu, Sunling; Yin, Jun-Jie; He, Weiwei; Lu, Wei; Ma, Ming; Gu, Ning; Zhang, Yu

    2016-05-11

    The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (•OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit •OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes. PMID:26918394

  12. Oxidative Folding: Cellular Strategies for Dealing with the Resultant Equimolar Production of Reactive Oxygen Species

    PubMed Central

    Shimizu, Yuichiro

    2009-01-01

    Abstract All eukaryotic cells possess an endoplasmic reticulum (ER), which is the site for synthesizing proteins that populate the cell surface or extracellular space. The environment of the ER is oxidizing, which supports the formation of intra- and interchain disulfide bonds that serve to stabilize the folding and assembly of nascent proteins. Recent experimental data reveal that the formation of disulfide bonds does not occur spontaneously but results from the enzymatic transfer of disulfide bonds through a number of intermediate proteins, with molecular oxygen serving as the terminal electron acceptor. Thus, each disulfide bond that forms during oxidative folding should produce a single reactive oxygen species (ROS). Dedicated secretory tissues like the pancreas and plasma cells have been estimated to form up to 3–6 million disulfide bonds per minute, which would be expected to result in the production of the same number of molecules of ROS. Although the methods used to deal with this amount of oxidative stress are not well understood, recent research suggests that different types of cells use distinct strategies and that the unfolded protein response (UPR) is a critical component of the defense. Antioxid. Redox Signal. 11, 2317–2331. PMID:19243234

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Scavenging of reactive oxygen species by some nonsteroidal anti-inflammatory drugs and fenofibrate.

    PubMed

    Kładna, Aleksandra; Aboul-Enein, Hassan Y; Kruk, Irena; Lichszteld, Krzysztof; Michalska, Teresa

    2006-06-01

    Ketoprofen and tolmetin are widely used nonsteroidal anti-inflammatory drugs, whereas fenofibrate belongs to a family of hypolipidemic drugs used in the prevention of cardiovascular diseases. The aim of this study was to assess effect of these drugs on reactions generating reactive oxygen species (ROS). The following generators of ROS were used: 18-crown-6/KO(2) dissolved in DMSO as a source of superoxide radical (O(.-)(2), the Fenton-like reaction (Cu/H(2)O(2)) for hydroxyl radical (HO(.)), 2,2'-azobis (2-amidino-propane) dichloride (AAPH) as peroxyl radical (ROO(.)) generator, and a mixture of alkaline aqueous H(2)O(2) and acetonitrile for singlet oxygen ((1)O(2)). Measurements were done using chemiluminescence, fluorescence, and spin-trapping with 2,2,6,6-tetramethylpiperidine combined with electron spin resonance spectroscopy (ESR), and a deoxyribose assay based on the spectrophotometry. The results obtained demonstrated that all tested drugs were active against O(.-)(2). There was a clear ranking of drug inhibition effects on chemiluminescence from the O(.-)(2) system: ketoprofen > tolmetin > fenofibrate. The examined compounds inhibited the HO(.)-dependent deoxyribose degradation and scavenged the ROO(.) concentration dependently with an order of potencies similar to that of the superoxide radical system. Hence, these results indicate that the studied drugs show broad ROS scavenging property and, as a consequence, might decrease tissue damage due to the ROS and thus to contribute to anti-inflammatory therapy. PMID:16245331

  16. Interconnection of reactive oxygen species chemistry across the interfaces of atmospheric, environmental, and biological processes.

    PubMed

    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 the environment, but they can also originate endogenously, initiated by electron reduction of molecular oxygen. These molecules have important biological signaling activities, but they cause oxidative stress when dysfunction within the antioxidant system occurs. Excess ROS in living organisms can lead to problems, such as protein oxidation-through either cleavage of the polypeptide chain or modification of amino acid side chains-and lipid oxidation. PMID:25688469

  17. Mitochondrial production of reactive oxygen species mediate dicumarol-induced cytotoxicity in cancer cells.

    PubMed

    Du, Juan; Daniels, David H; Asbury, Carla; Venkataraman, Sujatha; Liu, Jingru; Spitz, Douglas R; Oberley, Larry W; Cullen, Joseph J

    2006-12-01

    Dicumarol is a naturally occurring anticoagulant derived from coumarin that induces cytotoxicity and oxidative stress in human pancreatic cancer cells (Cullen, J. J., Hinkhouse, M. M., Grady, M., Gaut, A. W., Liu, J., Zhang, Y., Weydert, C. J. D., Domann, F. E., and Oberley, L. W. (2003) Cancer Res. 63, 5513-5520). Although dicumarol has been used as an inhibitor of the two-electron reductase NAD(P)H:quinone oxidoreductase (NQO1), dicumarol is also thought to affect quinone-mediated electron transfer reactions in the mitochondria, leading to the production of superoxide (O2*-) and hydrogen peroxide (H(2)O(2)). We hypothesized that mitochondrial production of reactive oxygen species mediates the increased susceptibility of pancreatic cancer cells to dicumarol-induced metabolic oxidative stress. Dicumarol decreased clonogenic survival equally in both MDA-MB-468 NQO1(-) and MDA-MB-468 NQO1+ breast cancer cells. Dicumarol decreased clonogenic survival in the transformed fibroblast cell line IMRSV-90 compared with the IMR-90 cell line. Dicumarol, with the addition of mitochondrial electron transport chain blockers, decreased clonogenic cell survival in human pancreatic cancer cells and increased superoxide levels. Dicumarol with the mitochondrial electron transport chain blocker antimycin A decreased clonogenic survival and increased superoxide levels in cells with functional mitochondria but had little effect on cancer cells without functional mitochondria. Overexpression of manganese superoxide dismutase and mitochondrial-targeted catalase with adenoviral vectors reversed the dicumarol-induced cytotoxicity and reversed fluorescence of the oxidation-sensitive probe. We conclude mitochondrial production of reactive oxygen species mediates the increased susceptibility of cancer cells to dicumarol-induced cytotoxicity. PMID:17040906

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

    SciTech Connect

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian

    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.

  19. Induction of reactive oxygen species in marine phytoplankton under crude oil exposure.

    PubMed

    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. PMID:26206126

  20. Oxygen isotopes in tree rings show good coherence between species and sites in Bolivia

    NASA Astrophysics Data System (ADS)

    Baker, Jessica C. A.; Hunt, Sarah F. P.; Clerici, Santiago J.; Newton, Robert J.; Bottrell, Simon H.; Leng, Melanie J.; Heaton, Timothy H. E.; Helle, Gerhard; Argollo, Jaime; Gloor, Manuel; Brienen, Roel J. W.

    2015-10-01

    A tree ring oxygen isotope (δ18OTR) chronology developed from one species (Cedrela odorata) growing in a single site has been shown to be a sensitive proxy for rainfall over the Amazon Basin, thus allowing reconstructions of precipitation in a region where meteorological records are short and scarce. Although these results suggest that there should be large-scale (> 100 km) spatial coherence of δ18OTR records in the Amazon, this has not been tested. Furthermore, it is of interest to investigate whether other, possibly longer-lived, species similarly record interannual variation of Amazon precipitation, and can be used to develop climate sensitive isotope chronologies. In this study, we measured δ18O in tree rings from seven lowland and one highland tree species from Bolivia. We found that cross-dating with δ18OTR gave more accurate tree ring dates than using ring width. Our "isotope cross-dating approach" is confirmed with radiocarbon "bomb-peak" dates, and has the potential to greatly facilitate development of δ18OTR records in the tropics, identify dating errors, and check annual ring formation in tropical trees. Six of the seven lowland species correlated significantly with C. odorata, showing that variation in δ18OTR has a coherent imprint across very different species, most likely arising from a dominant influence of source water δ18O on δ18OTR. In addition we show that δ18OTR series cohere over large distances, within and between species. Comparison of two C. odorata δ18OTR chronologies from sites several hundreds of kilometres apart showed a very strong correlation (r = 0.80, p < 0.001, 1901-2001), and a significant (but weaker) relationship was found between lowland C. odorata trees and a Polylepis tarapacana tree growing in the distant Altiplano (r = 0.39, p < 0.01, 1931-2001). This large-scale coherence of δ18OTR records is probably triggered by a strong spatial coherence in precipitation δ18O due to large-scale controls. These results highlight the strength of δ18OTR as a precipitation proxy, and open the way for temporal and spatial expansion of precipitation reconstructions in South America.

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

    PubMed

    Kazama, Makoto; Sato, Taizo; Hino, Akiya

    2014-05-01

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

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

    PubMed

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

    2013-02-01

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

  3. Reactive oxygen and nitrogen species as intracellular signals in skeletal muscle

    PubMed Central

    Powers, Scott K; Talbert, Erin E; Adhihetty, Peter J

    2011-01-01

    Abstract It is well established that contracting skeletal muscles produce free radicals. Given that radicals are known to play a prominent role in the pathogenesis of several diseases, the 1980s–90s dogma was that contraction-induced radical production was detrimental to muscle because of oxidative damage to macromolecules within the fibre. In contrast to this early outlook, it is now clear that both reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in cell signalling pathways involved in muscle adaptation to exercise and the remodelling that occurs in skeletal muscle during periods of prolonged inactivity. This review will highlight two important redox sensitive signalling pathways that contribute to ROS and RNS-induced skeletal muscle adaptation to endurance exercise. We begin with a historical overview of radical production in skeletal muscles followed by a discussion of the intracellular sites for ROS and RNS production in muscle fibres. We will then provide a synopsis of the redox-sensitive NF-κB and PGC-1α signalling pathways that contribute to skeletal muscle adaptation in response to exercise training. We will conclude with a discussion of unanswered questions in redox signalling in skeletal muscle in the hope of promoting additional research interest in this field. PMID:21224240

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2014-07-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  7. The NSAIDs indomethacin and diflunisal as scavengers of photogenerated reactive oxygen species.

    PubMed

    Purpora, Rebeca; Massad, Walter; Ferrari, Gabriela; Reynoso, Eugenia; Criado, Susana; Miskoski, Sandra; Pajares, Adriana; García, Norman A

    2013-01-01

    Diflunisal (DFNS) and Indomethacin (IMTC) are two profusely employed NSAIDs that provide anti-inflammatory and analgesic effects in humans. The scavenging of reactive oxygen species (ROS) by both NSAIDs was systematically studied in pH 7 aqueous solution. The ROS O2 ((1)Δg), O2(•-) and H2O2, generated by visible light irradiation of Riboflavin (Rf) in the presence of DFNS and IMTC, are deactivated by the NSAIDs. The ROS scavenging action by both NSAIDs constitutes an interesting result and adds one more positive aspect to the beneficial actions attributed to these drugs. Nevertheless it should be taken into account that several NSAIDs, in particular IMTC, have been connected to the pathogenesis of gastric mucosal lesions, which in some cases includes ROS generating-ability. DFNS quenches ROS in a dominant physical fashion. It constitutes an excellent protective-antioxidant provided that is practically not destroyed/oxidized after the ROS scavenging action. IMTC, being also an efficient interceptor of ROS, belong to the so-called group of sacrificial-ROS quenchers: It is easily degraded by the oxidative species in the scavenging action. Although this property is negative in the context of prolonged ROS elimination, exhibits a promissory aspect for the degradation of pharmaceutical contaminants, such as NSAIDs, in waste waters. PMID:23789718

  8. Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

    PubMed Central

    Mantena, Sudheer K; King, Adrienne L; Andringa, Kelly K; Landar, Aimee; Darley-Usmar, Victor; Bailey, Shannon M

    2007-01-01

    Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies. Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease. PMID:17854139

  9. Role of reactive oxygen species in age-related neuromuscular deficits.

    PubMed

    Jackson, Malcolm J; McArdle, Anne

    2016-04-15

    Although it is now clear that reactive oxygen species (ROS) are not the key determinants of longevity, a number of studies have highlighted the key role that these species play in age-related diseases and more generally in determining individual health span. Age-related loss of skeletal muscle mass and function is a key contributor to physical frailty in older individuals and our current understanding of the key areas in which ROS contribute to age-related deficits in muscle is through defective redox signalling and key roles in maintenance of neuromuscular integrity. This topical review will describe how ROS stimulate adaptations to contractile activity in muscle that include up-regulation of short-term stress responses, an increase in mitochondrial biogenesis and an increase in some catabolic processes. These adaptations occur through stimulation of redox-regulated processes that lead to the activation of transcription factors such as NF-κB, AP-1 and HSF1 which mediate changes in gene expression. They are attenuated during ageing and this appears to occur through an age-related increase in mitochondrial hydrogen peroxide production. The potential for redox-mediated cross-talk between motor neurons and muscle is also described to illustrate how ROS released from muscle fibres during exercise may help maintain the integrity of axons and how the degenerative changes in neuromuscular structure that occur with ageing may contribute to mitochondrial ROS generation in skeletal muscle fibres. PMID:26870901

  10. Imaging mitochondrial reactive oxygen species with fluorescent probes: current applications and challenges.

    PubMed

    Zhang, X; Gao, F

    2015-04-01

    Mitochondrial reactive oxygen species (ROS) is a key element in the regulation of several physiological functions and in the development or progression of multiple pathological events. A key task in the study of mitochondrial ROS is to establish reliable methods for measuring the ROS level in mitochondria with high selectivity, sensitivity, and spatiotemporal resolution. Over the last decade, imaging tools with fluorescent indicators from either small-molecule dyes or genetically encoded probes that can be targeted to mitochondria have been developed, which provide a powerful method to visualize and even quantify mitochondrial ROS level not only in live cells, but also in live animals. These innovative tools that have bestowed exciting new insights in mitochondrial ROS biology have been further promoted with the invention of new techniques in indicator design and fluorescent detection. However, these probes present some limitations in terms of specificity, sensitivity, and kinetics; failure to recognize these limitations often results in inappropriate interpretations of data. This review evaluates the recent advances in mitochondrial ROS imaging approaches with emphasis on their proper application and limitations, and highlights the future perspectives in the development of novel fluorescent probes for visualizing all species of ROS. PMID:25789762

  11. Synergistic effect of active oxygen species and alginate on chitinase production by Wasabia japonica cells and its application.

    PubMed

    Akimoto, C; Aoyagi, H; Dicosmo, F; Tanaka, H

    2000-01-01

    The specific chitinase productivity of a Wasabia japonica cell suspension culture under pure oxygen aeration was 3.8 times higher than that of a suspension culture aerated with ordinary air. During aeration with pure oxygen, both oxygen consumption by the cells and the H2O2 concentration in the medium increased. Addition of H2O2 to the cultivation medium also promoted the specific chitinase productivity. H2O2 could pass freely through the cell membrane. It was assumed that the excess oxygen was converted into active oxygen species such as H2O2, and that the promotion of chitinase production was probably due to the generated active oxygen species. Addition of alginate oligomer (AO, an endogenous elicitor-like substance) to cultures aerated with pure oxygen or supplemented with H2O2 resulted in synergistic increases in chitinase production. Based on these results, the development of a simple and efficient chitinase production system was investigated. Cells were immobilized in alginate gel (instead of adding AO to the medium) and cultivated in a medium containing H2O2. The specific chitinase productivity increased to the levels observed in the suspension culture system. During repeated batch cultivation of immobilized cells, the chitinase production remained stable for three repeated batches. When immobilized protoplasts were cultivated in a medium containing H2O2, there was 7-fold increase in chitinase production compared with that of immobilized cells. PMID:16232715

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

    NASA Astrophysics Data System (ADS)

    Krasnopolsky, V. A.

    2012-12-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  16. Mechanism of intestinal lipoprotein overproduction in insulin resistant humans.

    PubMed

    Duez, Hélène; Pavlic, Mirjana; Lewis, Gary F

    2008-09-01

    Triglyceride-rich lipoproteins (TRLs) derived from the intestine are increased in insulin resistant states both in the post-prandial and fasted state and are associated with increased cardiovascular risk. Impaired clearance has long been invoked to explain this accumulation of intestinal TRLs, but more recent studies have highlighted the fact that the production rate of apolipoprotein (apo) B-48-containing particles is also increased in insulin resistance and Type 2 diabetes. Recent data also indicate that the enterocyte, similar to the hepatocyte, overproduces lipoprotein particles in response to an elevation of plasma free fatty acids. It is not yet clear precisely how much this overproduction of intestinal lipoprotein particles contributes to the hypertriglyceridemia of insulin resistant states. We speculate that chronic intestinal overproduction of apoB-48 primes the intestine to rapidly and efficiently facilitate the absorption of ingested fat, enhancing the assembly and secretion of intestinal TRL, and hence contributing to post-prandial lipemia. PMID:18676184

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

    SciTech Connect

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

    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.

  18. Reactive oxygen species are involved in nickel inhibition of dna repair

    SciTech Connect

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

    1997-06-01

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

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

    PubMed

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

    2013-05-01

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

  20. Oxidative DNA adducts after Cu(2+)-mediated activation of dihydroxy PCBs: role of reactive oxygen species.

    PubMed

    Spencer, Wendy A; Lehmler, Hans-Joachim; Robertson, Larry W; Gupta, Ramesh C

    2009-05-15

    Polychlorinated biphenyls (PCBs) are toxic industrial chemicals, complete carcinogens, and efficacious tumor promoters. However, the mechanism(s) of PCB-mediated carcinogenicity remains largely undefined. One likely pathway by which these agents may play a role in carcinogenesis is the generation of oxidative DNA damage by redox cycling of dihydroxylated PCB metabolites. We have now employed a new (32)P-postlabeling system to examine novel oxidative DNA lesions induced by Cu(2+)-mediated activation of PCB metabolites. (32)P postlabeling of DNA incubated with various PCB metabolites resulted in over a dozen novel polar oxidative DNA adducts that were chromatographically similar for all active agents. The most potent metabolites tested were the hydroquinones (hydroxyl groups arranged para to each other), yielding polar oxidative adduct levels ranging from 55 to 142 adducts/10(6) nucleotides. PCB catechols, or ortho-dihydroxy metabolites, were up to 40% less active than their corresponding hydroquinone congeners, whereas monohydroxylated and quinone metabolites did not produce detectable oxidative damage over that of vehicle. With the exception of 2,4,5-Cl-2',5'-dihydroxybiphenyl, this oxidative DNA damage seemed to be inversely related to chlorine content: no chlorine approximately mono->di->trichlorinated metabolites. Importantly, copper, but not iron, was essential for activation of the PCB metabolites to these polar oxidative DNA adducts, because in its absence or in the presence of the Cu(+)-specific scavenger bathocuproine, no adducts were detected. Intervention studies with known reactive oxygen species (ROS) modifiers suggested that H(2)O(2), singlet oxygen, hydroxyl radical, and superoxide may also be involved in this PCB-mediated oxidative DNA damage. These data indicate a mechanistic role for several ROS, in addition to copper, in PCB-induced DNA damage and provide further support for oxidative DNA damage in PCB-mediated carcinogenesis. PMID:19233261

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

    PubMed

    Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

    2014-01-01

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

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

    PubMed Central

    Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

    2014-01-01

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

  3. Enhanced reactive oxygen species metabolism of air space cells in hypersensitivity pneumonitis

    SciTech Connect

    Calhoun, W.J. )

    1991-06-01

    Reactive oxygen species (ROS) are produced by phagocytic cells as part of host defense mechanisms, but these same products released by air space cells have been shown to contribute to pulmonary inflammation in interstitial lung diseases and likely represent a general mechanism of lung injury. However, the possible contribution of these compounds to lung inflammation in hypersensitivity pneumonitis (HP) has yet to be reported. We performed 11 bronchoalveolar lavage (BAL) studies in six patients with HP and compared the results with results from studies in 21 healthy normal volunteers. In patients with HP, spontaneous and stimulated measures of ROS metabolism by air space cells were significantly higher than those seen in normal volunteers. When alveolar macrophages were purified by depleting neutrophils and eosinophils on density gradients of Percoll (specific gravity 1.075 gm/ml), ROS metabolism remained elevated when compared with that in cells obtained from healthy controls, confirming that alveolar macrophage ROS metabolism is enhanced in patients with HP. Further, we found significant elevations in BAL total protein, lymphocytes, eosinophils, and neutrophils in patients with HP when they were compared with normal volunteers, with an increased proportion of BAL T lymphocytes expressing CD8 and natural killer surface antigens, consistent with previous work. Lavage samples from patients with HP with clinically active disease had higher proportions of BAL eosinophils and concentrations of total protein, lower forced expiratory volume in 1 second, lower forced vital capacity, and lower arterial oxygen tensions, and higher indices of ROS metabolism than samples from patients with HP with inactive disease. HP is associated with evidence of air space inflammation, to which alveolar macrophage-derived ROS may contribute.

  4. Hyperoxia-induced reactive oxygen species formation in pulmonary capillary endothelial cells in situ.

    PubMed

    Brueckl, Corinna; Kaestle, Stephanie; Kerem, Alexander; Habazettl, Helmut; Krombach, Fritz; Kuppe, Hermann; Kuebler, Wolfgang M

    2006-04-01

    Lung capillary endothelial cells (ECs) are a critical target of oxygen toxicity and play a central role in the pathogenesis of hyperoxic lung injury. To determine mechanisms and time course of EC activation in normobaric hyperoxia, we measured endothelial concentration of reactive oxygen species (ROS) and cytosolic calcium ([Ca(2+)](i)) by in situ imaging of 2',7'-dichlorofluorescein (DCF) and fura 2 fluorescence, respectively, and translocation of the small GTPase Rac1 by immunofluorescence in isolated perfused rat lungs. Endothelial DCF fluorescence and [Ca(2+)](i) increased continuously yet reversibly during a 90-min interval of hyperoxic ventilation with 70% O(2), demonstrating progressive ROS generation and second messenger signaling. ROS formation increased exponentially with higher O(2) concentrations. ROS and [Ca(2+)](i) responses were blocked by the mitochondrial complex I inhibitor rotenone, whereas inhibitors of NAD(P)H oxidase and the intracellular Ca(2+) chelator BAPTA predominantly attenuated the late phase of the hyperoxia-induced DCF fluorescence increase after > 30 min. Rac1 translocation in lung capillary ECs was barely detectable at normoxia but was prominent after 60 min of hyperoxia and could be blocked by rotenone and BAPTA. We conclude that hyperoxia induces ROS formation in lung capillary ECs, which initially originates from the mitochondrial electron transport chain but subsequently involves activation of NAD(P)H oxidase by endothelial [Ca(2+)](i) signaling and Rac1 activation. Our findings demonstrate rapid activation of ECs by hyperoxia in situ and identify mechanisms that may be relevant in the initiation of hyperoxic lung injury. PMID:16357365

  5. Robust DNA Damage Response and Elevated Reactive Oxygen Species in TINF2-Mutated Dyskeratosis Congenita Cells

    PubMed Central

    Pereboeva, Larisa; Hubbard, Meredith; Goldman, Frederick D.; Westin, Erik R.

    2016-01-01

    Dyskeratosis Congenita (DC) is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF) syndromes, converges on the DNA damage response (DDR) pathway and subsequent elevation of reactive oxygen species (ROS). Historically, DC patients have had poor outcomes following bone marrow transplantation (BMT), perhaps as a consequence of an underlying DNA hypersensitivity to cytotoxic agents. Previously, we demonstrated an activated DDR and increased ROS, augmented by chemotherapy and radiation, in somatic cells isolated from DC patients with a mutation in the RNA component of telomerase, TERC. The current study was undertaken to determine whether previous findings related to ROS and DDR in TERC patients’ cells could be extended to other DC mutations. Of particular interest was whether an antioxidant approach could counter increased ROS and decrease DC pathologies. To test this, we examined lymphocytes from DC patients from different DC mutations (TERT, TINF2, and TERC) for the presence of an active DDR and increased ROS. All DC mutations led to increased steady-state p53 (2-fold to 10-fold) and ROS (1.5-fold to 2-fold). Upon exposure to ionizing radiation (XRT), DC cells increased in both DDR and ROS to a significant degree. Exposing DC cells to hydrogen peroxide also revealed that DC cells maintain a significant oxidant burden compared to controls (1.5-fold to 3-fold). DC cell culture supplemented with N-acetylcysteine, or alternatively grown in low oxygen, afforded significant proliferative benefits (proliferation: maximum 2-fold increase; NAC: 5-fold p53 decrease; low oxygen: maximum 3.5-fold p53 decrease). Together, our data supports a mechanism whereby telomerase deficiency and subsequent shortened telomeres initiate a DDR and create a pro-oxidant environment, especially in cells carrying the TINF2 mutations. Finally, the ameliorative effects of antioxidants in vitro suggest this could translate to therapeutic benefits in DC patients. PMID:26859482

  6. Robust DNA Damage Response and Elevated Reactive Oxygen Species in TINF2-Mutated Dyskeratosis Congenita Cells.

    PubMed

    Pereboeva, Larisa; Hubbard, Meredith; Goldman, Frederick D; Westin, Erik R

    2016-01-01

    Dyskeratosis Congenita (DC) is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF) syndromes, converges on the DNA damage response (DDR) pathway and subsequent elevation of reactive oxygen species (ROS). Historically, DC patients have had poor outcomes following bone marrow transplantation (BMT), perhaps as a consequence of an underlying DNA hypersensitivity to cytotoxic agents. Previously, we demonstrated an activated DDR and increased ROS, augmented by chemotherapy and radiation, in somatic cells isolated from DC patients with a mutation in the RNA component of telomerase, TERC. The current study was undertaken to determine whether previous findings related to ROS and DDR in TERC patients' cells could be extended to other DC mutations. Of particular interest was whether an antioxidant approach could counter increased ROS and decrease DC pathologies. To test this, we examined lymphocytes from DC patients from different DC mutations (TERT, TINF2, and TERC) for the presence of an active DDR and increased ROS. All DC mutations led to increased steady-state p53 (2-fold to 10-fold) and ROS (1.5-fold to 2-fold). Upon exposure to ionizing radiation (XRT), DC cells increased in both DDR and ROS to a significant degree. Exposing DC cells to hydrogen peroxide also revealed that DC cells maintain a significant oxidant burden compared to controls (1.5-fold to 3-fold). DC cell culture supplemented with N-acetylcysteine, or alternatively grown in low oxygen, afforded significant proliferative benefits (proliferation: maximum 2-fold increase; NAC: 5-fold p53 decrease; low oxygen: maximum 3.5-fold p53 decrease). Together, our data supports a mechanism whereby telomerase deficiency and subsequent shortened telomeres initiate a DDR and create a pro-oxidant environment, especially in cells carrying the TINF2 mutations. Finally, the ameliorative effects of antioxidants in vitro suggest this could translate to therapeutic benefits in DC patients. PMID:26859482

  7. Negative feedback regulation of reactive oxygen species on AT1 receptor gene expression

    PubMed Central

    Nickenig, Georg; Strehlow, Kerstin; Bäumer, Anselm T; Baudler, Stefanie; Waßmann, Sven; Sauer, Heinrich; Böhm, Michael

    2000-01-01

    Free radicals as well as the AT1 receptor are involved in the pathogenesis of cardiovascular disease. Both the intracellular mechanisms of AT1 receptor regulation and the effect of free radicals on AT1 receptor expression are currently unknown. This study investigates the role of free radicals in the modulation of AT1 receptor expression and in the angiotensin II-induced AT1 receptor regulation. AT1 receptor mRNA was assessed by Northern blotting and AT1 receptor density by radioligand binding assays, respectively, in vascular smooth muscle cells (VSMC). Free radical release was measured by confocal laser scanning microscopy. AT1 receptor mRNA transcription rate was determined by nuclear run-on assays and AT1 receptor mRNA half-life was measured under transcriptional blockade. Angiotensin II caused a time-dependent decrease of AT1 receptor mRNA expression in rat VSMC in culture (30±6% at 4 h with 100 nM angiotensin II). This was followed by a consistent decrease in AT1 receptor density. Angiotensin II caused release of reactive oxygen species in VSMC which was abolished by preincubation with 100 μM diphenylene iodonium (DPI). DPI inhibited partially the down-regulating effect of angiotensin II on the AT1 receptor. Incubation of VSMC with either hydrogen peroxide or xanthine/xanthine oxidase caused a dose-dependent decrease in AT1 receptor mRNA expression which was not mediated by a decreased rate of transcription but rather through destabilization of AT1 receptor mRNA. Experiments which included preincubation of VSMC with various intracellular inhibitors suggested that free radicals caused AT1 receptor downregulation through activation of p38-MAP kinase and intracellular release of calcium. However, angiotensin II-induced AT1 receptor expression was not inhibited by blockade of p38-MAP kinase activation or intracellular calcium release. Free radicals may at least in part mediate angiotensin II-induced AT1 receptor regulation through direct post-transcriptional effects on AT1 receptor mRNA expression which involves intracellular release of calcium and activation of p38-MAP kinase. These findings may help to clarify the intracellular mechanisms involved in AT1 receptor regulation and reveal a novel biological feature for reactive oxygen species. PMID:11030730

  8. The extracellular A-loop of dual oxidases affects the specificity of reactive oxygen species release.

    PubMed

    Ueyama, Takehiko; Sakuma, Megumi; Ninoyu, Yuzuru; Hamada, Takeshi; Dupuy, Corinne; Geiszt, Miklós; Leto, Thomas L; Saito, Naoaki

    2015-03-01

    NADPH oxidase (Nox) family proteins produce superoxide (O2 (⨪)) directly by transferring an electron to molecular oxygen. Dual oxidases (Duoxes) also produce an O2 (⨪) intermediate, although the final species secreted by mature Duoxes is H2O2, suggesting that intramolecular O2 (⨪) dismutation or other mechanisms contribute to H2O2 release. We explored the structural determinants affecting reactive oxygen species formation by Duox enzymes. Duox2 showed O2 (⨪) leakage when mismatched with Duox activator 1 (DuoxA1). Duox2 released O2 (⨪) even in correctly matched combinations, including Duox2 + DuoxA2 and Duox2 + N-terminally tagged DuoxA2 regardless of the type or number of tags. Conversely, Duox1 did not release O2 (⨪) in any combination. Chimeric Duox2 possessing the A-loop of Duox1 showed no O2 (⨪) leakage; chimeric Duox1 possessing the A-loop of Duox2 released O2 (⨪). Moreover, Duox2 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA2 showed enhanced O2 (⨪) release, and Duox1 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA1 acquired O2 (⨪) leakage. Although we identified Duox1 A-loop residues (His(1071), His(1072), and Gly(1074)) important for reducing O2 (⨪) release, mutations of these residues to those of Duox2 failed to convert Duox1 to an O2 (⨪)-releasing enzyme. Using immunoprecipitation and endoglycosidase H sensitivity assays, we found that the A-loop of Duoxes binds to DuoxA N termini, creating more stable, mature Duox-DuoxA complexes. In conclusion, the A-loops of both Duoxes support H2O2 production through interaction with corresponding activators, but complex formation between the Duox1 A-loop and DuoxA1 results in tighter control of H2O2 release by the enzyme complex. PMID:25586178

  9. Isoform- and Species-specific Control of Inositol 1,4,5-Trisphosphate (IP3) Receptors by Reactive Oxygen Species*

    PubMed Central

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

    2014-01-01

    Reactive oxygen species (ROS) stimulate cytoplasmic [Ca2+] ([Ca2+]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2⨪) on IP3R-mediated Ca2+ signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca2+]c spikes and frequency-modulated oscillations evoked by a O2⨪ donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. The [Ca2+]c signal was mediated by ER Ca2+ mobilization. X+XO added to permeabilized cells promoted the [Ca2+]c rise evoked by submaximal doses of IP3, indicating that O2⨪ directly sensitizes IP3R-mediated Ca2+ release. In response to X+XO, DT40 cells lacking two of three IP3R isoforms (DKO) expressing either type 1 (DKO1) or type 2 IP3Rs (DKO2) showed a [Ca2+]c signal, whereas DKO expressing type 3 IP3R (DKO3) did not. By contrast, IgM that stimulates IP3 formation, elicited a [Ca2+]c signal in every DKO. X+XO also facilitated the Ca2+ release evoked by submaximal IP3 in permeabilized DKO1 and DKO2 but was ineffective in DKO3 or in DT40 lacking every IP3R (TKO). However, X+XO could also facilitate the effect of suboptimal IP3 in TKO transfected with rat IP3R3. Although in silico studies failed to identify a thiol missing in the chicken IP3R3, an X+XO-induced redox change was documented only in the rat IP3R3. Thus, ROS seem to specifically sensitize IP3Rs through a thiol group(s) within the IP3R, which is probably inaccessible in the chicken IP3R3. PMID:24469450

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

    PubMed

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

    2014-03-21

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

  11. The allelochemical L-DOPA increases melanin production and reduces reactive oxygen species in soybean roots.

    PubMed

    Soares, Anderson Ricardo; de Lourdes Lucio Ferrarese, Maria; de Cássia Siqueira-Soares, Rita; Marchiosi, Rogério; Finger-Teixeira, Aline; Ferrarese-Filho, Osvaldo

    2011-08-01

    The non-protein amino acid, L-3,4-dihydroxyphenylalanine (L-DOPA), is the main allelochemical released from the roots of velvetbean and affects seed germination and root growth of several plant species. In the work presented here, we evaluated, in soybean roots, the effects of L-DOPA on the following: polyphenol oxidase (PPO), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities; superoxide anion (O·-2), hydrogen peroxide (H(2)O(2)), and melanin contents; and lipid peroxidation. To this end, 3-day-old seedlings were cultivated in half-strength Hoagland's solution (pH 6.0), with or without 0.1 to 1.0 mM L-DOPA in a growth chamber (at 25°C, with a light/dark photoperiod of 12/12 hr and a photon flux density of 280 μmol m(-2) s(-1)) for 24 hr. The results showed that L-DOPA increased the PPO activity and, further, the melanin content. The activities of SOD and POD increased, but CAT activity decreased after the chemical exposure. The contents of reactive oxygen species (ROS), such as O·-2 and H(2)O(2), and the levels of lipid peroxidation significantly decreased under all concentrations of L-DOPA tested. These results suggest that L-DOPA was absorbed by the soybean roots and metabolized to melanin. It was concluded that the reduction in the O·-2 and H(2)O(2) contents and lipid peroxidation in soybean roots was due to the enhanced SOD and POD activities and thus a possible antioxidant role of L-DOPA. PMID:21710366

  12. Studies of Hematopoietic Cell Differentiation with a Ratiometric and Reversible Sensor of Mitochondrial Reactive Oxygen Species

    PubMed Central

    Kaur, Amandeep; Jankowska, Karolina; Pilgrim, Chelsea; Fraser, Stuart T.

    2016-01-01

    Abstract Aims: Chronic elevations in cellular redox state are known to result in the onset of various pathological conditions, but transient increases in reactive oxygen species (ROS)/reactive nitrogen species (RNS) are necessary for signal transduction and various physiological functions. There is a distinct lack of reversible fluorescent tools that can aid in studying and unraveling the roles of ROS/RNS in physiology and pathology by monitoring the variations in cellular ROS levels over time. In this work, we report the development of ratiometric fluorescent sensors that reversibly respond to changes in mitochondrial redox state. Results: Photophysical studies of the developed flavin–rhodamine redox sensors, flavin–rhodamine redox sensor 1 (FRR1) and flavin–rhodamine redox sensor 2 (FRR2), confirmed the reversible response of the probes upon reduction and re-oxidation over more than five cycles. The ratiometric output of FRR1 and FRR2 remained unaltered in the presence of other possible cellular interferants (metals and pH). Microscopy studies indicated clear mitochondrial localization of both probes, and FRR2 was shown to report the time-dependent increase of mitochondrial ROS levels after lipopolysaccharide stimulation in macrophages. Moreover, it was used to study the variations in mitochondrial redox state in mouse hematopoietic cells at different stages of embryonic development and maturation. Innovation: This study provides the first ratiometric and reversible probes for ROS, targeted to the mitochondria, which reveal variations in mitochondrial ROS levels at different stages of embryonic and adult blood cell production. Conclusions: Our results suggest that with their ratiometric and reversible outputs, FRR1 and FRR2 are valuable tools for the future study of oxidative stress and its implications in physiology and pathology. Antioxid. Redox Signal. 24, 667–679. PMID:26865422

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

    PubMed Central

    Schulz, Eberhard; Wenzel, Philip; Münzel, Thomas

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species

    PubMed Central

    Arjunan, Krishna Priya; Friedman, Gary; Fridman, Alexander; Clyne, Alisa Morss

    2012-01-01

    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. PMID:21653568

  16. Effect of reactive oxygen species on lysosomal membrane integrity. A study on a lysosomal fraction.

    PubMed

    Zdolsek, J M; Svensson, I

    1993-01-01

    Using a lysosome-enriched "light mitochondrial" fraction of a rat liver homogenate, the effects of the reactive oxygen species hydrogen peroxide, superoxide- and hydroxyl radicals were determined. Alterations in the intralysosomal pH and the release of a lysosomal marker enzyme, N-acetyl-glucosaminidase, were used as indicators of changes in the lysosomal membrane integrity. Lipid peroxidation of the fraction was assayed by TBARS measurement. Neither superoxide radicals, generated by hypoxanthine/xanthine oxidase, nor a bolus dose of hydrogen peroxide (0.5-1.5 mM) induced any lysosomal damage. If, however, Fe(III)ADP was included in the superoxide radical-generating system, lysosomal membrane damage was detected, both as an increase in lysosomal pH and as a release of N-acetyl-glucosaminidase, but only after a lag phase of about 7 min. Lipid peroxidation, on the other hand, proceeded gradually. Lysosomes treated with hydrogen peroxide displayed similar dose-dependent alterations, albeit only if both Fe(III)ADP and the reducing amino acid cysteine were added. In the latter system, however, alterations of the lysosomal membrane stability occurred more rapidly, showing a lag phase of only 2 min. Lipid peroxidation, which proceeded faster and displayed no lag phase, levelled out within 10 min. The results indicate that neither superoxide radicals nor hydrogen peroxide are by themselves damaging to lysosomes. Available catalytically active iron in Fe(II) form, however, allows reactions yielding powerful oxidative species--probably hydroxyl radicals formed via Fenton reactions--to take place inducing peroxidation of the lysosomal membranes resulting in dissipation of the proton-gradient and leakage of their enzyme contents. PMID:8148962

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

    NASA Astrophysics Data System (ADS)

    Louis, Kacie M.

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

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

    NASA Astrophysics Data System (ADS)

    Krasnopolsky, Vladimir A.

    2012-12-01

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

  19. Arginine Decarboxylase expression, polyamines biosynthesis and reactive oxygen species during organogenic nodule formation in hop.

    PubMed

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

    2011-02-01

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

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

    PubMed

    Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D; Boucher, Jeremie; Lee, Kevin Y; Lombard, David; Verdin, Eric M; Kahn, C Ronald

    2011-08-30

    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. PMID:21873205

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

    PubMed Central

    Baker, Mark A; Aitken, R John

    2005-01-01

    Human spermatozoa generate low levels of reactive oxygen species in order to stimulate key events, such as tyrosine phosphorylation, associated with sperm capacitation. However, if the generation of these potentially pernicious oxygen metabolites becomes elevated for any reason, spermatozoa possess a limited capacity to protect themselves from oxidative stress. As a consequence, exposure of human spermatozoa to intrinsically- or extrinsically- generated reactive oxygen intermediates can result in a state of oxidative stress characterized by peroxidative damage to the sperm plasma membrane and DNA damage to the mitochondrial and nuclear genomes. Oxidative stress in the male germ line is associated with poor fertilization rates, impaired embryonic development, high levels of abortion and increased morbidity in the offspring, including childhood cancer. In this review, we consider the possible origins of oxidative damage to human spermatozoa and reflect on the important contribution such stress might make to the origins of genetic disease in our species. PMID:16313680

  2. Effect of reactive oxygen species (ROS) generating system for control of airborne microorganisms in meat processing environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effectiveness of reactive oxygen species (ROS) generating AirOcare equipment on the reduction of airborne bacteria in a meat processing environment was determined. Serratia marcescens and lactic acid bacteria (Lactococcus lactis subsp. lactis and Lactobacillus plantarum) were used to artificiall...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Using fluorescence-activated flow cytometry to determine reactive oxygen species formation and membrane lipid peroxidation in viable boar spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluorescence-activated flow cytometry analyses were developed for determination of reactive oxygen species (ROS) formation and membrane lipid peroxidation in live spermatozoa loaded with, respectively, hydroethidine (HE) or the lipophilic probe 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-d...

  5. Generation of Reactive Oxygen and Anti-Oxidant Species by Hydrodynamically-Stressed Suspensions of Morinda citrofolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The generation of reactive oxygen species (ROS) by plant cell suspension cultures, in response to the imposition of both biotic and abiotic stress, is well-documented. This study investigated the generation of hydrogen peroxide by hydrodynamically-stressed cultures of Morinda citrifolia, over a 5-ho...

  6. Eicosanoids up-regulate production of reactive oxygen species by NADPH-dependent oxidase in Spodoptera exigua phagocytic hemocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eicosanoids mediate cellular immune responses in insects, including phagocytosis of invading microbes. Phagocytosis entails two major steps, the internalization of microbes and the subsequent killing of them via formation of reactive oxygen species (ROS). Here, we posed the hypothesis that eicosanoi...

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

    EPA Science Inventory

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

  8. Study of the photochemically generated of oxygen species by fullerene photosensitized CoS{sub 2} nanocompounds

    SciTech Connect

    Meng, Ze-Da; Zhu, Lei; Ullah, Kefayat; Ye, Shu; Sun, Qian; Jang, Won Kweon; Oh, Won-Chun

    2014-01-01

    Graphical abstract: - Highlights: Reactive oxygen species was detected through oxidation reaction from DPCI to DPCO. Generated reactive oxygen species and hydroxyl radicals can be analysis by DPCI degradation. C{sub 60} has good effect during the photo-degradation processes. Photocatalytic activity attributed to photo-absorption effect by C{sub 60} and cooperative effect of CoS{sub 2}. - Abstract: Reactive oxygen species (ROS) can be produced by interactions between sunlight and light-absorbing substance in natural water environment and can completely destroy various organic pollutants in wastewaters. In this study, CoS{sub 2} and CoS{sub 2}fullerene were irradiated by visible light respectively. The generation of reactive oxygen species were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). In comparison with the separate effects of CoS{sub 2} and fullerene nanoparticles, the photochemically effect of the fullerene photosensitized CoS{sub 2} composites is increased significantly due to the synergetic effect between the fullerene and the CoS{sub 2} nanoparticles.

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

    SciTech Connect

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

    2009-08-15

    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.

  10. The development and in vitro characterisation of an intracellular nanosensor responsive to reactive oxygen species.

    PubMed

    Henderson, James R; Fulton, David A; McNeil, Calum J; Manning, Philip

    2009-08-15

    Advances in sensor technologies have enhanced our understanding of the roles played by reactive oxygen species (ROS) in a number of physiological and pathological processes. However, high inter-reactivity and short life spans has made real-time monitoring of ROS in cellular systems challenging. Fluorescent dyes capable of intracellular ROS measurements have been reported. However, these dyes are known to be intrinsically cytotoxic and thus can potentially significantly alter cellular metabolism and adversely influence in vitro data. Reported here is the development and in vitro application of a novel ROS responsive nanosensor, based on PEBBLE (Probes Encapsulated By Biologically Localised Embedding) technology. The ROS sensitive fluorescent probe dihydrorhodamine 123 (DHR 123) was employed as the sensing element of the PEBBLE through entrapment within a porous, bio-inert polyacrylamide nanostructure enabling passive monitoring of free radical flux within the intracellular environment. Successful delivery of the nanosensors into NR8383 rat alveolar macrophage cells via phagocytosis was achieved. Stimulation of PEBBLE loaded NR8383 cells with phorbol-12-myristate-13-acetate (PMA) enabled real time monitoring of ROS generation within the cell without affecting cellular viability. These data suggest that PEBBLE nanosensors could offer significant advantages over existing technologies used in monitoring the intracellular environment. PMID:19553099

  11. Correlation between cell migration and reactive oxygen species under electric field stimulation.

    PubMed

    Wu, Shang-Ying; Hou, Hsien-San; Sun, Yung-Shin; Cheng, Ji-Yen; Lo, Kai-Yin

    2015-09-01

    Cell migration is an essential process involved in the development and maintenance of multicellular organisms. Electric fields (EFs) are one of the many physical and chemical factors known to affect cell migration, a phenomenon termed electrotaxis or galvanotaxis. In this paper, a microfluidics chip was developed to study the migration of cells under different electrical and chemical stimuli. This chip is capable of providing four different strengths of EFs in combination with two different chemicals via one simple set of agar salt bridges and Ag/AgCl electrodes. NIH 3T3 fibroblasts were seeded inside this chip to study their migration and reactive oxygen species (ROS) production in response to different EF strengths and the presence of β-lapachone. We found that both the EF and β-lapachone level increased the cell migration rate and the production of ROS in an EF-strength-dependent manner. A strong linear correlation between the cell migration rate and the amount of intracellular ROS suggests that ROS are an intermediate product by which EF and β-lapachone enhance cell migration. Moreover, an anti-oxidant, α-tocopherol, was found to quench the production of ROS, resulting in a decrease in the migration rate. PMID:26487906

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

    PubMed

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-08-24

    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. PMID:22877754

  13. A novel nematode effector suppresses plant immunity by activating host reactive oxygen species-scavenging system.

    PubMed

    Lin, Borong; Zhuo, Kan; Chen, Shiyan; Hu, Lili; Sun, Longhua; Wang, Xiaohong; Zhang, Lian-Hui; Liao, Jinling

    2016-02-01

    Evidence is emerging that plant-parasitic nematodes can secrete effectors to interfere with the host immune response, but it remains unknown how these effectors can conquer host immune responses. Here, we depict a novel effector, MjTTL5, that could suppress plant immune response. Immunolocalization and transcriptional analyses showed that MjTTL5 is expressed specifically within the subventral gland of Meloidogyne javanica and up-regulated in the early parasitic stage of the nematode. Transgenic Arabidopsis lines expressing MjTTL5 were significantly more susceptible to M. javanica infection than wild-type plants, and vice versa, in planta silencing of MjTTL5 substantially increased plant resistance to M. javanica. Yeast two-hybrid, coimmunoprecipitation and bimolecular fluorescent complementation assays showed that MjTTL5 interacts specifically with Arabidopsis ferredoxin : thioredoxin reductase catalytic subunit (AtFTRc), a key component of host antioxidant system. The expression of AtFTRc is induced by the infection of M. javanica. Interaction between AtFTRc and MjTTL could drastically increase host reactive oxygen species-scavenging activity, and result in suppression of plant basal defenses and attenuation of host resistance to the nematode infection. Our results demonstrate that the host ferredoxin : thioredoxin system can be exploited cunningly by M. javanica, revealing a novel mechanism utilized by plant-parasitic nematodes to subjugate plant innate immunity and thereby promoting parasitism. PMID:26484653

  14. Reactive oxygen species induced by shear stress mediate cell death in Bacillus subtilis.

    PubMed

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

    2006-05-01

    Exposure of Bacillus subtilis to a shear rate of 1,482/s leads to a rapid loss of cell viability after 10 h of growth. Biochemical and molecular evidences provided below strongly suggest that cell death under high shear results from an apoptosis-like process similar to that described in eukaryotes, with activation of a caspase-3-like protease (C(3)LP) followed by DNA fragmentation. Shear stress leads to an increase in specific intracellular reactive oxygen species (siROS), possibly through activation of NADH oxidase (NOX). The formation of siROS precedes the activation of C(3)LP and DNA fragmentation, thus establishing siROS as the molecular link between shear stress and apoptosis-like cell death. A model is proposed in which NOX is viewed as being strategically placed on the plasma membrane of B. subtilis that senses and converts a mechanical force arising from shear stress into a chemical signal leading to activation of C(3)LP, DNA fragmentation, and thus, apoptosis-like cell death. PMID:16570320

  15. Neuroprotection by Polynitrogen Manganese Complexes: Regulation of Reactive Oxygen Species-Related Pathways.

    PubMed

    Chen, Chunxia; Cao, Jing; Ma, Xiaoyan; Wang, Xiaobo; Chen, Qiuyun; Yan, Shihai; Zhao, Ningwei; Geng, Zhirong; Wang, Zhilin

    2016-01-01

    Cell death in the central nervous system causes neurologic diseases, in which reactive oxygen species (ROS) play a critical role by either inducing cellular oxidative stress or by increasing the cell tolerance against insult. Neurologic diseases may potentially be treated by regulating ROS levels in a certain range with small molecules. We studied preconditioning with two polynitrogen manganese complexes (1 and 2) to regulate intracellular ROS levels in the protection of both the differentiated rat pheochromocytoma cell line (PC12 cells) and neurons against H2O2-induced apoptosis. Pre-treatment with the two complexes attenuated the cell apoptosis caused by H2O2. And the ROS-related neuroprotective mechanisms were explored. Both complexes activate the hypoxia inducible factor-related pathways and increase the cell adaptation to oxidative stress. Pre-treatment with complex 1 eliminated intracellular ROS, which also activated antioxidase system, while short-term incubation of complex 2, generated low levels of ROS leading to cell survival. PMID:26857964

  16. Lycopene induces apoptosis in Candida albicans through reactive oxygen species production and mitochondrial dysfunction.

    PubMed

    Choi, Hyemin; Lee, Dong Gun

    2015-08-01

    Lycopene, a well-known carotenoid pigment found in tomatoes, has shown various biological functions. In our previous report, we showed that lycopene induces two apoptotic hallmarks, plasma membrane depolarization and G2/M cell cycle arrest, in Candida albicans. In this study, we investigated the ability of lycopene to induce apoptosis, and the mechanism by which it regulates apoptosis. FITC-Annexin V staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, and 4',6-diamidino-2-phenylindole (DAPI) assay showed that lycopene exerted its antifungal activity during the early and late stages of apoptosis in C. albicans. During apoptosis, intracellular reactive oxygen species (ROS) were increased, and specifically the hydroxyl radicals contributed to the fungal cell death. Furthermore, lycopene treatment caused intracellular Ca(2+) overload and mitochondrial dysfunction, such as mitochondrial depolarization and cytochrome c release from the mitochondria to the cytoplasm. At last caspase activation was triggered. In summary, lycopene exerted its antifungal effects against C. albicans by inducing apoptosis via ROS production and mitochondrial dysfunction. PMID:26005097

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

    PubMed

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

    2014-10-30

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

  18. Reactive Oxygen Species-Dependent Cell Signaling Regulates the Mosquito Immune Response to Plasmodium falciparum

    PubMed Central

    Surachetpong, Win; Pakpour, Nazzy; Cheung, Kong Wai

    2011-01-01

    Abstract Reactive oxygen species (ROS) have been implicated in direct killing of pathogens, increased tissue damage, and regulation of immune signaling pathways in mammalian cells. Available research suggests that analogous phenomena affect the establishment of Plasmodium infection in Anopheles mosquitoes. We have previously shown that provision of human insulin in a blood meal leads to increased ROS levels in Anopheles stephensi. Here, we demonstrate that provision of human insulin significantly increased parasite development in the same mosquito host in a manner that was not consistent with ROS-induced parasite killing or parasite escape through damaged tissue. Rather, our studies demonstrate that ROS are important mediators of both the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling branches of the mosquito insulin signaling cascade. Further, ROS alone can directly activate these signaling pathways and this activation is growth factor specific. Our data, therefore, highlight a novel role for ROS as signaling mediators in the mosquito innate immune response to Plasmodium parasites. Antioxid. Redox Signal. 14, 943955. PMID:21126166

  19. CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia.

    PubMed

    Parajuli, Bijay; Horiuchi, Hiroshi; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

    2015-12-01

    The chemokine CCL11 (also known as eotaxin-1) is a potent eosinophil chemoattractant that mediates allergic diseases such as asthma, atopic dermatitis, and inflammatory bowel diseases. Previous studies demonstrated that concentrations of CCL11 are elevated in the sera and cerebrospinal fluids (CSF) of patients with neuroinflammatory disorders, including multiple sclerosis. Moreover, the levels of CCL11 in plasma and CSF increase with age, and CCL11 suppresses adult neurogenesis in the central nervous system (CNS), resulting in memory impairment. However, the precise source and function of CCL11 in the CNS are not fully understood. In this study, we found that activated astrocytes release CCL11, whereas microglia predominantly express the CCL11 receptor. CCL11 significantly promoted the migration of microglia, and induced microglial production of reactive oxygen species by upregulating nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), thereby promoting excitotoxic neuronal death. These effects were reversed by inhibition of NOX1. Our findings suggest that CCL11 released from activated astrocytes triggers oxidative stress via microglial NOX1 activation and potentiates glutamate-mediated neurotoxicity, which may be involved in the pathogenesis of various neurological disorders. PMID:26184677

  20. Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function

    PubMed Central

    Khoory, Joseph; Estanislau, Jessica; Elkhal, Abdallah; Lazaar, Asmae; Melhorn, Mark I.; Brodsky, Abigail; Illigens, Ben; Hamachi, Itaru; Kurishita, Yasutaka; Ivanov, Alexander R.; Shevkoplyas, Sergey; Shapiro, Nathan I.; Ghiran, Ionita C.

    2016-01-01

    Acute, inflammatory conditions associated with dysregulated complement activation are characterized by significant increases in blood concentration of reactive oxygen species (ROS) and ATP. The mechanisms by which these molecules arise are not fully understood. In this study, using luminometric- and fluorescence-based methods, we show that ligation of glycophorin A (GPA) on human red blood cells (RBCs) results in a 2.1-fold, NADPH-oxidase-dependent increase in intracellular ROS that, in turn, trigger multiple downstream cascades leading to caspase-3 activation, ATP release, and increased band 3 phosphorylation. Functionally, using 2D microchannels to assess membrane deformability, GPS-ligated RBCs travel 33% slower than control RBCs, and lipid mobility was hindered by 10% using fluorescence recovery after photobleaching (FRAP). These outcomes were preventable by pretreating RBCs with cell-permeable ROS scavenger glutathione monoethyl ester (GSH-ME). Our results obtained in vitro using anti-GPA antibodies were validated using complement-altered RBCs isolated from control and septic patients. Our results suggest that during inflammatory conditions, circulating RBCs significantly contribute to capillary flow dysfunctions, and constitute an important but overlooked source of intravascular ROS and ATP, both critical mediators responsible for endothelial cell activation, microcirculation impairment, platelet activation, as well as long-term dysregulated adaptive and innate immune responses. PMID:26784696

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

    PubMed

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

    2014-10-01

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

  2. The bright side of reactive oxygen species: lifespan extension without cellular demise

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Oxidative stress and the generation of reactive oxygen species (ROS) can lead to mitochondrial dysfunction, DNA damage, protein misfolding, programmed cell death with apoptosis and autophagy, and the promotion of aging –dependent processes. Mitochondria control the processing of redox energy that yields adenosine triphosphate (ATP) through the oxidation of glucose, pyruvate, and nicotinamide adenine dinucleotide. Ultimately, the generation of ROS occurs with the aerobic production of ATP. Although reduced levels of ROS may lead to tolerance against metabolic, mechanical, and oxidative stressors and the generation of brief periods of ROS during ischemia-reperfusion models may limit cellular injury, under most circumstances ROS and mitochondrial dysfunction can lead to apoptotic caspase activation and autophagy induction that can result in cellular demise. Yet, new work suggests that ROS generation may have a positive impact through respiratory complex I reverse electron transport that can extend lifespan. Such mechanisms may bring new insight into clinically relevant disorders that are linked to cellular senescence and aging of the body’s system. Further investigation of the potential “bright side” of ROS and mitochondrial respiration is necessary to target specific pathways, such as the mechanistic target of rapamycin, nicotinamidases, sirtuins, mRNA decoupling and protein expression, and Wnt signaling, that can impact oxidative stress-ROS mechanisms to extend lifespan and eliminate disease onset. PMID:27200181

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

    Exogenous electric fields have been implied in cardiac differentiation of mouse embryonic stem cells and the generation of reactive oxygen species (ROS). In this work, we explored the effects of electrical field stimulation on ROS generation and cardiogenesis in embryoid bodies (EBs) derived from human embryonic stem cells (hESC, line H13), using a custom-built electrical-stimulation bioreactor. Electrical properties of the bioreactor system were characterized by electrochemical impedance spectroscopy (EIS) and analysis of electrical currents. The effects of the electrode material (stainless steel, titanium-nitride coated titanium, titanium), length of stimulus (1 s and 90 s) and age of EBs at the onset of electrical stimulation (4 and 8 days) were investigated with respect to ROS generation. The amplitude of the applied electrical field was 1 V/mm. The highest rate of ROS generation was observed for stainless steel electrodes, for signal duration of 90 s, and 4-days old EBs. Notably, comparable ROS generation was achieved by incubation of EBs with 1 nM H2O2. Cardiac differentiation in these EBs was evidenced by spontaneous contractions, expression of Troponin T, and its sarcomeric organization. These results imply that electrical stimulation plays a role in cardiac differentiation of hESCs, through mechanisms associated with the intracellular generation of ROS. PMID:19720058

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

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

    PubMed

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

    2015-02-01

    Nitric oxide (NO) has many functions in plants. Here, we investigated its interplays with reactive oxygen species (ROS) in the defence responses triggered by the elicitin cryptogein. The production of NO induced by cryptogein in tobacco cells was partly regulated through a ROS-dependent pathway involving the NADPH oxidase NtRBOHD. In turn, NO down-regulated the level of H2O2. Both NO and ROS synthesis appeared to be under the control of type-2 histone deacetylases acting as negative regulators of cell death. Occurrence of an interplay between NO and ROS was further supported by the finding that cryptogein triggered a production of peroxynitrite (ONOO(-)). Next, we showed that ROS, but not NO, negatively regulate the intensity of activity of the cryptogein-induced protein kinase NtOSAK. Furthermore, using a DNA microarray approach, we identified 15 genes early induced by cryptogein via NO. A part of these genes was also modulated by ROS and encoded proteins showing sequence identity to ubiquitin ligases. Their expression appeared to be negatively regulated by ONOO(-), suggesting that ONOO(-) mitigates the effects of NO and ROS. Finally, we provided evidence that NO required NtRBOHD activity for inducing cell death, thus confirming previous assumption that ROS channel NO through cell death pathways. PMID:24506708

  7. The role of reactive oxygen species and autophagy in safingol-induced cell death

    PubMed Central

    Ling, L-U; Tan, K-B; Lin, H; Chiu, G N C

    2011-01-01

    Safingol is a sphingolipid with promising anticancer potential, which is currently in phase I clinical trial. Yet, the underlying mechanisms of its action remain largely unknown. We reported here that safingol-induced primarily accidental necrotic cell death in MDA-MB-231 and HT-29 cells, as shown by the increase in the percentage of cells stained positive for 7-aminoactinomycin , collapse of mitochondria membrane potential and depletion of intracellular ATP. Importantly, safingol treatment produced time- and concentration-dependent reactive oxygen species (ROS) generation. Autophagy was triggered following safingol treatment, as reflected by the formation of autophagosomes, acidic vacuoles, increased light chain 3-II and Atg biomarkers expression. Interestingly, scavenging ROS with N-acetyl--cysteine could prevent the autophagic features and reverse safingol-induced necrosis. Our data also suggested that autophagy was a cell repair mechanism, as suppression of autophagy by 3-methyladenine or bafilomycin A1 significantly augmented cell death on 2-5 μ safingol treatment. In addition, Bcl-xL and Bax might be involved in the regulation of safingol-induced autophagy. Finally, glucose uptake was shown to be inhibited by safingol treatment, which was associated with an increase in p-AMPK expression. Taken together, our data suggested that ROS was the mediator of safingol-induced cancer cell death, and autophagy is likely to be a mechanism triggered to repair damages from ROS generation on safingol treatment. PMID:21390063

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2014-09-15

    Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes. PMID:24813286

  10. Myomir dysregulation and reactive oxygen species in aged human satellite cells.

    PubMed

    Di Filippo, Ester Sara; Mancinelli, Rosa; Pietrangelo, Tiziana; La Rovere, Rita Maria Laura; Quattrocelli, Mattia; Sampaolesi, Maurilio; Fulle, Stefania

    2016-04-29

    Satellite cells that reside on the myofibre surface are crucial for the muscle homeostasis and regeneration. Aging goes along with a less effective regeneration of skeletal muscle tissue mainly due to the decreased myogenic capability of satellite cells. This phenomenon impedes proper maintenance and contributes to the age-associated decline in muscle mass, known as sarcopenia. The myogenic potential impairment does not depend on a reduced myogenic cell number, but mainly on their difficulty to complete a differentiation program. The unbalanced production of reactive oxygen species in elderly people could be responsible for skeletal muscle impairments. microRNAs are conserved post-transcriptional regulators implicated in numerous biological processes including adult myogenesis. Here, we measure the ROS level and analyze myomiR (miR-1, miR-133b and miR-206) expression in human myogenic precursors obtained from Vastus lateralis of elderly and young subjects to provide the molecular signature responsible for the differentiation impairment of elderly activated satellite cells. PMID:26975470

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    2013-01-01

    Abstract Reactive oxygen species (ROS) exert various biological effects and contribute to signaling events during physiological and pathological processes. Enhanced levels of ROS are highly associated with different tumors, a Western lifestyle, and a nutritional regime. The supplementation of food with traditional antioxidants was shown to be protective against cancer in a number of studies both in vitro and in vivo. However, recent large-scale human trials in well-nourished populations did not confirm the beneficial role of antioxidants in cancer, whereas there is a well-established connection between longevity of several human populations and increased amount of antioxidants in their diets. Although our knowledge about ROS generators, ROS scavengers, and ROS signaling has improved, the knowledge about the direct link between nutrition, ROS levels, and cancer is limited. These limitations are partly due to lack of standardized reliable ROS measurement methods, easily usable biomarkers, knowledge of ROS action in cellular compartments, and individual genetic predispositions. The current review summarizes ROS formation due to nutrition with respect to macronutrients and antioxidant micronutrients in the context of cancer and discusses signaling mechanisms, used biomarkers, and its limitations along with large-scale human trials. Antioxid. Redox Signal. 19, 2157–2196. PMID:23458328

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

    SciTech Connect

    Jung, Se-Hui; Park, Jin-Young; Joo, Jung-Hoon; Kim, Young-Myeong; Ha, Kwon-Soo

    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.

  14. Mitochondrial reactive oxygen species modulate innate immune response to influenza A virus in human nasal epithelium.

    PubMed

    Kim, Sujin; Kim, Min-Ji; Park, Do Yang; Chung, Hyo Jin; Kim, Chang-Hoon; Yoon, Joo-Heon; Kim, Hyun Jik

    2015-07-01

    The innate immune system of the nasal epithelium serves as a first line of defense against invading respiratory viruses including influenza A virus (IAV). Recently, it was verified that interferon (IFN)-related immune responses play a critical role in local antiviral innate immunity. Reactive oxygen species (ROS) generation by exogenous pathogens has also been demonstrated in respiratory epithelial cells and modulation of ROS has been reported to be important for respiratory virus-induced innate immune mechanisms. Passage-2 normal human nasal epithelial (NHNE) cells were inoculated with IAV (WS/33, H1N1) to assess the sources of IAV-induced ROS and the relationship between ROS and IFN-related innate immune responses. Both STAT1 and STAT2 phosphorylation and the mRNA levels of IFN-stimulated genes, including Mx1, 2,5-OAS1, IFIT1, and CXCL10, were induced after IAV infection up to three days post infection. Similarly, we observed that mitochondrial ROS generation increased maximally at 2 days after IAV infection. After suppression of mitochondrial ROS generation, IAV-induced phosphorylation of STAT and mRNA levels of IFN-stimulated genes were attenuated and actually, viral titers of IAV were significantly higher in cases with scavenging ROS. Our findings suggest that mitochondrial ROS might be responsible for controlling IAV infection and may be potential sources of ROS generation, which is required to initiate an innate immune response in NHNE cells. PMID:25930096

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

    PubMed Central

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

    2014-01-01

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

  16. Reactive Oxygen Species as Additional Determinants for Cytotoxicity of Clostridium difficile Toxins A and B

    PubMed Central

    Frädrich, Claudia; Beer, Lara-Antonia; Gerhard, Ralf

    2016-01-01

    Clostridium difficile infections can induce mild to severe diarrhoea and the often associated characteristic pseudomembranous colitis. Two protein toxins, the large glucosyltransferases TcdA and TcdB, are the main pathogenicity factors that can induce all clinical symptoms in animal models. The classical molecular mode of action of these homologous toxins is the inhibition of Rho GTPases by mono-glucosylation. Rho-inhibition leads to breakdown of the actin cytoskeleton, induces stress-activated and pro-inflammatory signaling and eventually results in apoptosis of the affected cells. An increasing number of reports, however, have documented further qualities of TcdA and TcdB, including the production of reactive oxygen species (ROS) by target cells. This review summarizes observations dealing with the production of ROS induced by TcdA and TcdB, dissects pathways that contribute to this phenomenon and speculates about ROS in mediating pathogenesis. In conclusion, ROS have to be considered as a discrete, glucosyltransferase-independent quality of at least TcdB, triggered by different mechanisms. PMID:26797634

  17. Prevention of cytotoxicity of nickel by quercetin: the role of reactive oxygen species and histone acetylation.

    PubMed

    Chen, Jie; Han, Jia; Wang, Jianmin

    2013-05-01

    Excessive exposure to nickel may cause health effects on the blood, lung, nose, kidney, reproductive system, skin and the unborn child. In the present study, we found that Ni²⁺ exposure led to a time- and dose-dependent proliferation arrest and death in human leukemia HL-60 cells. In the presence of 1 mM Ni²⁺, reactive oxygen species (ROS) generation (indicated by the level of malondialdehyde) increased to 323% and histone acetylation decreased to 32%. Interestingly, quercetin (QU) dose dependently prevented Ni²⁺-induced cell proliferation arrest and death from 0 to 80 μM but showed similar activity of scavenging ROS at the concentrations of 20, 40 and 80 µM. When the effect of QU on histone acetylation was studied, QU significantly prevented Ni²⁺-induced histone hypoacetylation at 40 or 80 µM. Moreover, increase in histone acetylation by trichostatin A could also significantly enhance the protection effect of QU at 10 or 20 µM but not at higher concentrations. Thus, our results further confirmed the critical role of ROS and histone hypoacetylation in the cytotoxicity of Ni²⁺ exposure and proved that QU is a potentially useful native dietary compound to efficiently prevent Ni²⁺-caused cytotoxicity through both diminishing ROS generation and increasing histone acetylation. PMID:22294440

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

    SciTech Connect

    Kim, Ki Hyun; Park, Ju Yeol; Jung, Hye Jin; Kwon, Ho Jeong

    2011-01-07

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

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

    PubMed

    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. PMID:25624148

  20. Facile endothelial cell micropatterning induced by reactive oxygen species on polydimethylsiloxane substrates.

    PubMed

    Choi, Jong Seob; Kim, Do Hyun; Seo, Tae Seok

    2016-04-01

    Sophisticated cell pattern provides unique cellular assay platform for studying cell to cell interaction, cellular differentiation and signaling, high-throughput cell response to chemicals. In this study, we demonstrated reactive oxygen species (ROS) mediated endothelial cell micropatterning on a polydimethylsiloxane (PDMS) substrate. The exposure of UV/O radiation led to the formation of ROS on the surface of PDMS, which could selectively prevent adhesion of endothelial cells. The degree of ROS amount was monitored according to the UV/O irradiation time, and at least 36 μM of ROS resulted in the precise cellular micropattern on the PDMS. The presence of ROS affected not only cellular detachment from the substrate, but also endothelial cell morphology such as cell spreading area, confluence, nuclear area and nuclear inverse aspect ratio. In addition, we could observe that the actin cytoskeleton of cells was also constricted due to ROS, thereby minimizing the focal adhesion area of vinculin. Compared with previously reported methods which use chemical treatment or nano/microstructure on the substrate, the proposed methodology is quite simple, accurate, and harmless to the patterned endothelial cells. PMID:26852296

  1. Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling.

    PubMed

    Corcionivoschi, Nicolae; Alvarez, Luis A J; Sharp, Thomas H; Strengert, Monika; Alemka, Abofu; Mantell, Judith; Verkade, Paul; Knaus, Ulla G; Bourke, Billy

    2012-07-19

    Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling. PMID:22817987

  2. Ambient Fine Particulate Matter Induces Apoptosis of Endothelial Progenitor Cells Through Reactive Oxygen Species Formation

    PubMed Central

    Cui, Yuqi; Xie, Xiaoyun; Jia, Fengpeng; He, Jianfeng; Li, Zhihong; Fu, Minghuan; Hao, Hong; Liu, Ying; Liu, Jason Z.; Cowan, Peter J.; Zhu, Hua; Sun, Qinghua; Liu, Zhenguo

    2015-01-01

    Background/Aims Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in angiogenesis and vascular repair. Some environmental insults, like fine particulate matter (PM) exposure, significantly impair cardiovascular functions. However, the mechanisms for PM-induced adverse effects on cardiovascular system remain largely unknown. The present research was to study the detrimental effects of PM on EPCs and explore the potential mechanisms. Methods PM was intranasal-distilled into male C57BL/6 mice for one month. Flow cytometry was used to measure the number of EPCs, apoptosis level of circulating EPCs and intracellular reactive oxygen species (ROS) formation. Serum TNF-α and IL-1β were measured using ELISA. To determine the role of PM-induced ROS in EPC apoptosis, PM was co-administrated with the antioxidant N-acetylcysteine (NAC) in wild type mice or used in a triple transgenic mouse line (TG) with overexpression of antioxidant enzyme network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase (Gpx-1) with decreased in vivo ROS production. Results PM treatment significantly decreased circulating EPC population, promoted apoptosis of EPCs in association with increased ROS production and serum TNF-α and IL-1β levels, which could be effectively reversed by either NAC treatment or overexpression of AON. Conclusion PM exposure significantly decreased circulating EPCs population due to increased apoptosis via ROS formation in mice. PMID:25591776

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

    PubMed Central

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

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

  4. Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species.

    PubMed

    Han, Sang Jun; Jang, Hee-Seong; Kim, Jee In; Lipschutz, Joshua H; Park, Kwon Moo

    2016-01-01

    The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS). PMID:26923764

  5. High cell density attenuates reactive oxygen species: implications for in vitro assays.

    PubMed

    Kim, Dennis P; Yahav, Jonathan; Sperandeo, Michael; Maloney, Lauren; McTigue, Monica; Lin, Fubao; Clark, Richard A F

    2012-01-01

    In vitro cell-based assays are an essential and universally used step in elucidation of biological processes as well as in drug development. However, results obtained depend on the validity of protocols used. This statement certainly pertains to in vitro assays of oxidative stress. The holy grail of in vitro models is reliability and predictability of outcomes that relate to a single variable like addition of hydrogen peroxide or xanthine oxidase. Without such validated outcomes, comparison of results among different laboratories is not possible. Achieving this goal requires a thorough understanding of the complex interplay between the cells, their environment, and the experimental assays. Furthermore, as this knowledge is attained, it must be disseminated and used to update and standardize existing protocols. Here, we confirm and extend the effect of pyruvate and cell density on in vitro oxidative stress assays. Cell viability was assessed using a colorimetric assay measuring the reduction of a tetrazolium salt (XTT) into a colored formazan dye. Extracellular hydrogen peroxide concentrations were measured using the foxp3 assay. We confirmed a previously reported finding that pyruvate, a common ingredient in cell culture media, acts as an extracellular scavenger of reactive oxygen species. We also demonstrated that cell density directly correlates with resistance to oxidative stress in tissue culture. It is theorized that the protective effect due to cell density predominantly relates to intracellular factors such as reduced glutathione and extracellular factors such as catalase. PMID:22107255

  6. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    PubMed Central

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. PMID:26730190

  7. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

    PubMed Central

    Abe, Michiaki; Mori, Takefumi; O'Connor, Paul M.; Ohsaki, Yusuke; Zheleznova, Nadezhda N.

    2014-01-01

    The physiological evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na+ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension. PMID:25354941

  8. Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production.

    PubMed

    Ye, Junli; Jiang, Zhongxin; Chen, Xuehong; Liu, Mengyang; Li, Jing; Liu, Na

    2016-01-15

    Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation. PMID:26511505

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

    PubMed

    Zuo, Li; Motherwell, Michael S

    2013-12-10

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

  10. THE ROLE OF REACTIVE OXYGEN SPECIES IN TUMOR CELLS APOPTOSIS INDUCED BY LANDOMYCIN A.

    PubMed

    Lehka, L V; Panchuk, R R; Berger, W; Rohr, Ju; Stoika, R S

    2015-01-01

    Landomycin A (LA) is a new antitumor antibiotic of angucycline group, possessing high antitumor activity against cancer cells of different origin, which induces early apoptosis in target cells. It was shown that under LA action the level of reactive oxygen species (ROS) in human T-leukemia cells had increased 5.6 times in comparison to control already at the 1st hour after the addition of studied antibiotic to the culture medium. At the 6th hour after incubation of cells with LA the nucleosomal DNA cleavage, chromatin condensation and nucleus fragmentation were observed, indicating apoptotic cell death. Catalase (scavenger of hydrogen peroxide), mannitol (scavenger of hydroxyl radicals) and superoxide dismutase (scavenger of superoxide radicals) reduced the level of ROS production under LA, suggesting the generation of H2O2, OH* and O2- radicals, respectively. It was revealed that catalase and mannitol effectively inhibited LA-mediated tumor cell death, increasing 2.5 times the percentage of alive cells in comparison to LA. However, superoxide dismutase had no significant inhibitory effect on cytotoxic activity of LA, indicating the minor role of superoxide anions in the implementation of antitumor activity of this antibiotic. Combination of catalase, mannitol and superoxide dismutase with LA increased 4-fold the percentage of alive cells in comparison to the action of LA. Dynamics of ROS formation confirms that the increase of ROS is a very rapid process, but at the same time it is not a direct consequence of apoptosis triggering, mediated by mitochondria. PMID:26717598

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

    PubMed

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

    2014-01-01

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

  12. Generation of Reactive Oxygen Species via NOXa Is Important for Development and Pathogenicity of Mycosphaerella graminicola.

    PubMed

    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. PMID:27103853

  13. Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species

    PubMed Central

    Rebiger, Lars; Lenzen, Sigurd; Mehmeti, Ilir

    2016-01-01

    Brown adipose tissue (BAT) cells have a very high oxidative capacity. On the other hand, in obesity and obesity-related diabetes, levels of pro-inflammatory cytokines are elevated, which might promote BAT dysfunction and consequently impair carbohydrate metabolism and thereby exacerbate cellular dysfunction and promote diabetes progression. Therefore, the antioxidative enzyme status of a brown adipocyte cell line and its susceptibility towards pro-inflammatory cytokines, which participate in the pathogenesis of diabetes, and reactive oxygen species (ROS) were analysed. Mature brown adipocytes exhibited significantly higher levels of expression of mitochondrially and peroxisomally located antioxidative enzymes compared with non-differentiated brown adipocytes. Pro-inflammatory cytokines induced a significant decrease in the viability of differentiated brown adipocytes, which was accompanied by a massive ROS production and down-regulation of BAT-specific markers, such as uncoupling protein 1 (UCP-1) and β-Klotho. Taken together, the results strongly indicate that pro-inflammatory cytokines cause brown adipocyte dysfunction and death through suppression of BAT-specific proteins, especially of UCP-1 and β-Klotho, and consequently increased oxidative stress. PMID:26795216

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. Interplay between reactive oxygen species and hormones in the control of plant development and stress tolerance.

    PubMed

    Xia, Xiao-Jian; Zhou, Yan-Hong; Shi, Kai; Zhou, Jie; Foyer, Christine H; Yu, Jing-Quan

    2015-05-01

    As a consequence of a sessile lifestyle, plants are continuously exposed to changing environmental conditions and often life-threatening stresses caused by exposure to excessive light, extremes of temperature, limiting nutrient or water availability, and pathogen/insect attack. The flexible coordination of plant growth and development is necessary to optimize vigour and fitness in a changing environment through rapid and appropriate responses to such stresses. The concept that reactive oxygen species (ROS) are versatile signalling molecules in plants that contribute to stress acclimation is well established. This review provides an overview of our current knowledge of how ROS production and signalling are integrated with the action of auxin, brassinosteroids, gibberellins, abscisic acid, ethylene, strigolactones, salicylic acid, and jasmonic acid in the coordinate regulation of plant growth and stress tolerance. We consider the local and systemic crosstalk between ROS and hormonal signalling pathways and identify multiple points of reciprocal control, as well as providing insights into the integration nodes that involve Ca(2+)-dependent processes and mitogen-activated protein kinase phosphorylation cascades. PMID:25788732

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

    PubMed Central

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

    2013-01-01

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

  18. Arabidopsis CAP1-mediated ammonium sensing required reactive oxygen species in plant cell growth.

    PubMed

    Bai, Ling; Zhou, Yun; Ma, Xiaonan; Gao, Lijie; Song, Chun-Peng

    2014-06-18

    [Ca (2+)]cyt-associated protein kinase (CAP) gene 1 is a receptor-like kinase that belongs to CrRLK1L (Catharanthus roseus Receptor like kinase) subfamily. CAP1 has been identified as a novel modulator of NH 4(+) in the tonoplast, which regulates root hair growth by maintaining the cytoplasmic Ca (2+) gradients. Different expression pattern of tonoplast intrinsic protein (TIP2;3) in the CAP1 knock out mutant and wild type on Murashige and Skoog (MS) medium suggested that CAP1 influences transport activity to regulate the compartmentalization of NH 4(+) into vacuole. Lower expression level of Oxidative Signal-Inducible1(OXI1) in the cap1-1 root and the abnormal reactive oxygen species (ROS) gradient in root hair of cap1-1 on MS medium indicated that ROS signaling involve in CAP1-regulated root hair growth. Wild-type-like ROS distribution pattern in the cap1-1 root hair can be reestablished in seedlings grown on NH 4(+) deficient medium, which indicated that CAP1 functions as a sensor for NH 4(+) signaling in maintaining tip-focused ROS gradient in root hairs polar growth. PMID:24940875

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

    PubMed Central

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

    2014-01-01

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

  20. NADPH oxidases, reactive oxygen species, and the kidney: friend and foe.

    PubMed

    Sedeek, Mona; Nasrallah, Rania; Touyz, Rhian M; Hébert, Richard L

    2013-10-01

    Reactive oxygen species (ROS) play an important role in normal cellular physiology. They regulate different biologic processes such as cell defense, hormone synthesis and signaling, activation of G protein-coupled receptors, and ion channels and kinases/phosphatases. ROS are also important regulators of transcription factors and gene expression. On the other hand, in pathologic conditions, a surplus of ROS in tissue results in oxidative stress with various injurious consequences such as inflammation and fibrosis. NADPH oxidases are one of the many sources of ROS in biologic systems, and there are seven isoforms (Nox1-5, Duox1, Duox2). Nox4 is the predominant form in the kidney, although Nox2 is also expressed. Nox4 has been implicated in the basal production of ROS in the kidney and in pathologic conditions such as diabetic nephropathy and CKD; upregulation of Nox4 may be important in renal oxidative stress and kidney injury. Although there is growing evidence indicating the involvement of NADPH oxidase in renal pathology, there is a paucity of information on the role of NADPH oxidase in the regulation of normal renal function. Here we provide an update on the role of NADPH oxidases and ROS in renal physiology and pathology. PMID:23970124

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-07-01

    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 ClO2 (100 ppm).

  3. Reactive oxygen species involved in CT26 immunogenic cell death induced by Clostridium difficile toxin B.

    PubMed

    Sun, Chunli; Wang, Haiying; Mao, Shuang; Liu, Ji; Li, Shan; Wang, Jufang

    2015-04-01

    Immunogenic cell death (ICD) is a new concept appeared in recent years. Despite growing interests of research on ICD, the circumstances that trigger immune responses against dying tumor cells remain largely unknown. It was demonstrated that recombinant Clostridium difficile toxin B (rTcdB) can induce ICD in intoxicated cells, but its mechanism remains unclear. This work aims at exploring whether reactive oxygen species (ROS) involved in rTcdB induced ICD using the chemical agent N-acetyl cysteine (NAC), diphenylene iodonium (DPI) and Antimycin A (Anti.A). The results suggested that ROS involved in rTcdB induced apoptosis and autophagy. DPI and Anti.A successfully inhibited the antitumor immune effect induced by rTcdB. As ICD is determined by a variety of factors, rTcdB is a potential tool for further exploring the circumstances that trigger ICD, which may offer us a good choice for designing the new chemotherapeutic drugs with immunogenic properties. PMID:25721381

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

    PubMed Central

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

    2013-01-01

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

  5. Age-dependent action of reactive oxygen species on transmitter release in mammalian neuromuscular junctions.

    PubMed

    Shakirzyanova, Anastasia; Valeeva, Guzel; Giniatullin, Arthur; Naumenko, Nikolay; Fulle, Stefania; Akulov, Anton; Atalay, Mustafa; Nikolsky, Eugeny; Giniatullin, Rashid

    2016-02-01

    Reactive oxygen species (ROS) are implicated in aging, but the neurobiological mechanisms of ROS action are not fully understood. Using electrophysiological techniques and biochemical assays, we studied the age-dependent effect of hydrogen peroxide (H2O2) on acetylcholine release in rat diaphragm neuromuscular junctions. H2O2 significantly inhibited both spontaneous (measured as frequency of miniature end-plate potentials) and evoked (amplitude of end-plate potentials) transmitter release in adult rats. The inhibitory effect of H2O2 was much stronger in old rats, whereas in newborns tested during the first postnatal week, H2O2 did not affect spontaneous release from nerve endings and potentiated end-plate potentials. Proteinkinase C activation or intracellular Ca(2+) elevation restored redox sensitivity of miniature end-plate potentials in newborns. The resistance of neonates to H2O2 inhibition was associated with higher catalase and glutathione peroxidase activities in skeletal muscle. In contrast, the activities of these enzymes were downregulated in old rats. Our data indicate that the vulnerability of transmitter release to oxidative damage strongly correlates with aging and might be used as an early indicator of senescence. PMID:26827645

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

    SciTech Connect

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

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  8. TOR complex 2-Ypk1 signaling regulates actin polarization via reactive oxygen species.

    PubMed

    Niles, Brad J; Powers, Ted

    2014-12-01

    The evolutionarily conserved mTOR complex 2 (mTORC2) signaling pathway is an important regulator of actin cytoskeletal architecture and, as such, is a candidate target for preventing cancer cell motility and invasion. Remarkably, the precise mechanism(s) by which mTORC2 regulates the actin cytoskeleton have remained elusive. Here we show that in budding yeast, TORC2 and its downstream kinase Ypk1 regulate actin polarization by controlling reactive oxygen species (ROS) accumulation. Specifically, we find that TORC2-Ypk1 regulates actin polarization both by vacuole-related ROS, controlled by the phospholipid flippase kinase Fpk1 and sphingolipids, and by mitochondria-mediated ROS, controlled by the PKA subunit Tpk3. In addition, we find that the protein kinase C (Pkc1)/MAPK cascade, a well-established regulator of actin, acts downstream of Ypk1 to regulate ROS, in part by promoting degradation of the oxidative stress responsive repressor, cyclin C. Furthermore, we show that Ypk1 regulates Pkc1 activity through proper localization of Rom2 at the plasma membrane, which is also dependent on Fpk1 and sphingolipids. Together these findings demonstrate important links between TORC2/Ypk1 signaling, Fpk1, sphingolipids, Pkc1, and ROS as regulators of actin and suggest that ROS may play an important role in mTORC2-dependent dysregulation of the actin cytoskeleton in cancer cells. PMID:25253719

  9. p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation

    PubMed Central

    Jin, Huan; Yin, Shutao; Song, Xinhua; Zhang, Enxiang; Fan, Lihong; Hu, Hongbo

    2016-01-01

    Patulin is a major mycotoxin found in fungal contaminated fruits and their derivative products. Previous studies showed that patulin was able to induce increase of reactive oxygen species (ROS) generation and oxidative stress was suggested to play a pivotal role in patulin-induced multiple toxic signaling. The objective of the present study was to investigate the functional role of p53 in patulin-induced oxidative stress. Our study demonstrated that higher levels of ROS generation and DNA damage were induced in wild-type p53 cell lines than that found in either knockdown or knockout p53 cell lines in response to patulin exposure, suggesting p53 activation contributed to patulin-induced ROS generation. Mechanistically, we revealed that the pro-oxidant role of p53 in response to patulin was attributed to its ability to suppress catalase activity through up-regulation of PIG3. Moreover, these in vitro findings were further validated in the p53 wild-type/knockout mouse model. To the best of our knowledge, this is the first report addressing the functional role of p53 in patulin-induced oxidative stress. The findings of the present study provided novel insights into understanding mechanisms behind oxidative stress in response to patulin exposure. PMID:27071452

  10. p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation.

    PubMed

    Jin, Huan; Yin, Shutao; Song, Xinhua; Zhang, Enxiang; Fan, Lihong; Hu, Hongbo

    2016-01-01

    Patulin is a major mycotoxin found in fungal contaminated fruits and their derivative products. Previous studies showed that patulin was able to induce increase of reactive oxygen species (ROS) generation and oxidative stress was suggested to play a pivotal role in patulin-induced multiple toxic signaling. The objective of the present study was to investigate the functional role of p53 in patulin-induced oxidative stress. Our study demonstrated that higher levels of ROS generation and DNA damage were induced in wild-type p53 cell lines than that found in either knockdown or knockout p53 cell lines in response to patulin exposure, suggesting p53 activation contributed to patulin-induced ROS generation. Mechanistically, we revealed that the pro-oxidant role of p53 in response to patulin was attributed to its ability to suppress catalase activity through up-regulation of PIG3. Moreover, these in vitro findings were further validated in the p53 wild-type/knockout mouse model. To the best of our knowledge, this is the first report addressing the functional role of p53 in patulin-induced oxidative stress. The findings of the present study provided novel insights into understanding mechanisms behind oxidative stress in response to patulin exposure. PMID:27071452

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

    PubMed

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

    2015-02-01

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

  12. Metabolic regulation of the ultradian oscillator Hes1 by reactive oxygen species.

    PubMed

    Ventre, Simona; Indrieri, Alessia; Fracassi, Chiara; Franco, Brunella; Conte, Ivan; Cardone, Luca; di Bernardo, Diego

    2015-05-22

    Ultradian oscillators are cyclically expressed genes with a period of less than 24h, found in the major signalling pathways. The Notch effector hairy and enhancer of split Hes genes are ultradian oscillators. The physiological signals that synchronise and entrain Hes oscillators remain poorly understood. We investigated whether cellular metabolism modulates Hes1 cyclic expression. We demonstrated that, in mouse myoblasts (C2C12), Hes1 oscillation depends on reactive oxygen species (ROS), which are generated by the mitochondria electron transport chain and by NADPH oxidases NOXs. In vitro, the regulation of Hes1 by ROS occurs via the calcium-mediated signalling. The modulation of Hes1 by ROS was relevant in vivo, since perturbing ROS homeostasis was sufficient to alter Medaka (Oryzias latipes) somitogenesis, a process that is dependent on Hes1 ultradian oscillation during embryo development. Moreover, in a Medaka model for human microphthalmia with linear skin lesions syndrome, in which mitochondrial ROS homeostasis was impaired, we documented important somitogenesis defects and the deregulation of Hes homologues genes involved in somitogenesis. Notably, both molecular and developmental defects were rescued by antioxidant treatments. Our studies provide the first evidence of a coupling between cellular redox metabolism and an ultradian biological oscillator with important pathophysiological implication for somitogenesis. PMID:25796437

  13. Mitochondrial physiology and reactive oxygen species production are altered by hypoxia acclimation in killifish (Fundulus heteroclitus).

    PubMed

    Du, Sherry N N; Mahalingam, Sajeni; Borowiec, Brittney G; Scott, Graham R

    2016-04-15

    Many fish encounter hypoxia in their native environment, but the role of mitochondrial physiology in hypoxia acclimation and hypoxia tolerance is poorly understood. We investigated the effects of hypoxia acclimation on mitochondrial respiration, O2kinetics, emission of reactive oxygen species (ROS), and antioxidant capacity in the estuarine killifish ( ITALIC! Fundulus heteroclitus). Killifish were acclimated to normoxia, constant hypoxia (5 kPa O2) or intermittent diel cycles of nocturnal hypoxia (12 h:12 h normoxia:hypoxia) for 28-33 days and mitochondria were isolated from liver. Neither pattern of hypoxia acclimation affected the respiratory capacities for oxidative phosphorylation or electron transport, leak respiration, coupling control or phosphorylation efficiency. Hypoxia acclimation also had no effect on mitochondrial O2kinetics, but ITALIC! P50(the O2tension at which hypoxia inhibits respiration by 50%) was lower in the leak state than during maximal respiration, and killifish mitochondria endured anoxia-reoxygenation without any impact on mitochondrial respiration. However, both patterns of hypoxia acclimation reduced the rate of ROS emission from mitochondria when compared at a common O2tension. Hypoxia acclimation also increased the levels of protein carbonyls and the activities of superoxide dismutase and catalase in liver tissue (the latter only occurred in constant hypoxia). Our results suggest that hypoxia acclimation is associated with changes in mitochondrial physiology that decrease ROS production and may help improve hypoxia tolerance. PMID:26896545

  14. Effect of reactive oxygen species on the biosynthesis and structure of newly synthesized proteoglycans.

    PubMed

    Panasyuk, A; Frati, E; Ribault, D; Mitrovic, D

    1994-02-01

    The effect of reactive oxygen species (ROS) generated by a xanthine oxidase hypoxanthine system (mainly H2O2) on proteoglycan (PG) metabolism and structure was investigated in vitro, using cell monolayers of cultured rabbit articular chondrocytes and purified resident and newly synthesized proteoglycans. It was shown that ROS generated in this system frequently stimulate (at low concentrations), and consistently inhibit (at higher concentrations), the incorporation of 35SO4 and 3H-glucosamine into PG molecules synthesized by cultured chondrocytes. The inhibition of isotopes' incorporation at higher enzyme concentrations was suppressed completely by heating xanthine oxidase and allopurinol with superoxide dismutase (SOD) and catalase. ROS at high concentration also inhibited 3H-uridine incorporation but had no effect on 35SO4 and 3H-uridine uptake by the cells. They also alter hyaluronan (HA) and PG monomers by fragmenting the core protein moiety and destroying the hyaluronic acid binding region. Altered PG monomers do not interact with HA to form complexes, but fragmented HA still retain a significant PG monomer-binding capacity. PG-HA complexes are easily and irreversibly destroyed by ROS. These results suggest that ROS may at low fluxes stimulate PG-synthesis under physiological conditions and alter cartilage metabolism and structure in conditions where they are overproduced, such as in rheumatoid arthritis, and in hemochromatosis and other iron storage diseases. PMID:8005511

  15. Ethylene response factor 6 is a regulator of reactive oxygen species signaling in Arabidopsis.

    PubMed

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

    2013-01-01

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

  16. Peroxisomes contribute to reactive oxygen species homeostasis and cell division induction in Arabidopsis protoplasts.

    PubMed

    Tiew, Terence W-Y; Sheahan, Michael B; Rose, Ray J

    2015-01-01

    The ability to induce Arabidopsis protoplasts to dedifferentiate and divide provides a convenient system to analyze organelle dynamics in plant cells acquiring totipotency. Using peroxisome-targeted fluorescent proteins, we show that during protoplast culture, peroxisomes undergo massive proliferation and disperse uniformly around the cell before cell division. Peroxisome dispersion is influenced by the cytoskeleton, ensuring unbiased segregation during cell division. Considering their role in oxidative metabolism, we also investigated how peroxisomes influence homeostasis of reactive oxygen species (ROS). Protoplast isolation induces an oxidative burst, with mitochondria the likely major ROS producers. Subsequently ROS levels in protoplast cultures decline, correlating with the increase in peroxisomes, suggesting that peroxisome proliferation may also aid restoration of ROS homeostasis. Transcriptional profiling showed up-regulation of several peroxisome-localized antioxidant enzymes, most notably catalase (CAT). Analysis of antioxidant levels, CAT activity and CAT isoform 3 mutants (cat3) indicate that peroxisome-localized CAT plays a major role in restoring ROS homeostasis. Furthermore, protoplast cultures of pex11a, a peroxisome division mutant, and cat3 mutants show reduced induction of cell division. Taken together, the data indicate that peroxisome proliferation and CAT contribute to ROS homeostasis and subsequent protoplast division induction. PMID:26379686

  17. Reactive oxygen species and their role in plant defence and cell wall metabolism.

    PubMed

    O'Brien, Jose A; Daudi, Arsalan; Butt, Vernon S; Bolwell, G Paul

    2012-09-01

    Harnessing the toxic properties of reactive oxygen species (ROS) to fight off invading pathogens can be considered a major evolutionary success story. All aerobic organisms have evolved the ability to regulate the levels of these toxic intermediates, whereas some have evolved elaborate signalling pathways to dramatically increase the levels of ROS and use them as weapons in mounting a defence response, a process commonly referred to as the oxidative burst. The balance between steady state levels of ROS and the exponential increase in these levels during the oxidative burst has begun to shed light on complex signalling networks mediated by these molecules. Here, we discuss the different sources of ROS that are present in plant cells and review their role in the oxidative burst. We further describe two well-studied ROS generating systems, the NADPH oxidase and apoplastic peroxidase proteins, and their role as the primary producers of ROS during pathogen invasion. We then discuss what is known about the metabolic and proteomic fluxes that occur in plant cells during the oxidative burst and after pathogen recognition, and try to highlight underlying biochemical processes that may provide more insight on the complex regulation of ROS in plants. PMID:22767200

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

    PubMed

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

    2013-09-01

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

  19. Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage.

    PubMed

    Kim, Hojin; Lee, Gong-Rak; Kim, Jiwon; Baek, Jin Young; Jo, You-Jin; Hong, Seong-Eun; Kim, Sung Hoon; Lee, Jiae; Lee, Hye In; Park, Song-Kyu; Kim, Hwan Mook; Lee, Hwa Jeong; Chang, Tong-Shin; Rhee, Sue Goo; Lee, Ju-Seog; Jeong, Woojin

    2016-02-01

    Recent studies have shown that many types of cancer cells have increased levels of reactive oxygen species (ROS) and enhance antioxidant capacity as an adaptation to intrinsic oxidative stress, suggesting that cancer cells are more vulnerable to oxidative insults and are more dependent on antioxidant systems compared with normal cells. Thus, disruption of redox homeostasis caused by a decline in antioxidant capacity may provide a method for the selective death of cancer cells. Here we show that ROS-mediated selective death of tumor cells can be caused by inhibiting sulfiredoxin (Srx), which reduces hyperoxidized peroxiredoxins, leading to their reactivation. Srx inhibitor increased the accumulation of sulfinic peroxiredoxins and ROS, which led to oxidative mitochondrial damage and caspase activation, resulting in the death of A549 human lung adenocarcinoma cells. Srx depletion also inhibited the growth of A549 cells like Srx inhibition, and the cytotoxic effects of Srx inhibitor were considerably reversed by Srx overexpression or antioxidants such as N-acetyl cysteine and butylated hydroxyanisol. Moreover, Srx inhibitor rendered tumorigenic ovarian cells more susceptible to ROS-mediated death compared with nontumorigenic cells and significantly suppressed the growth of A549 xenografts without acute toxicity. Our results suggest that Srx might serve as a novel therapeutic target for cancer treatment based on ROS-mediated cell death. PMID:26721593

  20. Arabidopsis CAP1-mediated ammonium sensing required reactive oxygen species in plant cell growth

    PubMed Central

    Bai, Ling; Zhou, Yun; Ma, Xiaonan; Gao, Lijie; Song, Chun-Peng

    2014-01-01

    [Ca2+]cyt-associated protein kinase (CAP) gene 1 is a receptor-like kinase that belongs to CrRLK1L (Catharanthus roseus Receptor like kinase) subfamily. CAP1 has been identified as a novel modulator of NH4+ in the tonoplast, which regulates root hair growth by maintaining the cytoplasmic Ca2+ gradients. Different expression pattern of tonoplast intrinsic protein (TIP2;3) in the CAP1 knock out mutant and wild type on Murashige and Skoog (MS) medium suggested that CAP1 influences transport activity to regulate the compartmentalization of NH4+ into vacuole. Lower expression level of Oxidative Signal-Inducible1(OXI1) in the cap1-1 root and the abnormal reactive oxygen species (ROS) gradient in root hair of cap1-1 on MS medium indicated that ROS signaling involve in CAP1-regulated root hair growth. Wild-type-like ROS distribution pattern in the cap1-1 root hair can be reestablished in seedlings grown on NH4+ deficient medium, which indicated that CAP1 functions as a sensor for NH4+ signaling in maintaining tip-focused ROS gradient in root hairs polar growth. PMID:25763633

  1. Extracellular production of reactive oxygen species during seed germination and early seedling growth in Pisum sativum.

    PubMed

    Kranner, Ilse; Roach, Thomas; Beckett, Richard P; Whitaker, Claire; Minibayeva, Farida V

    2010-07-01

    Extracellularly produced reactive oxygen species (ROS) play key roles in plant development, but their significance for seed germination and seedling establishment is poorly understood. Here we report on the characteristics of extracellular ROS production during seed germination and early seedling development in Pisum sativum. Extracellular superoxide (O2(.-)) and hydrogen peroxide (H2O2) production and the activity of extracellular peroxidases (ECPOX) were determined spectrophotometrically, and O2(.-) was identified by electron paramagnetic resonance. Cell wall fractionation of cotyledons, seed coats and radicles was used in conjunction with polyacrylamide gel electrophoresis to investigate substrate specificity and molecular masses of O2(.-)-producing enzymes, and the forces that bind them to the cell wall. Seed imbibition was accompanied by an immediate, transient burst of redox activity that involved O2(.-) and other substances capable of oxidizing epinephrine, and also H2O2. At the final stages of germination, coinciding with radicle elongation, a second increase in O2(.-) but not H2O2 production occurred and was correlated with an increase in extracellular ECPOX activity. Electrophoretic analyses of cell wall fractions demonstrated the presence of enzymes capable of O2(.-) production. The significance of extracellular ROS production during seed germination and early seedling development, and also during seed aging, is discussed. PMID:20303611

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    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. PMID:25576869

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

    PubMed Central

    Sewelam, Nasser; Kazan, Kemal; Schenk, Peer M.

    2016-01-01

    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. PMID:26941757

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

    Allan, A. C.; Fluhr, R.

    1997-01-01

    Reactive oxygen species (ROS) play a prominent role in early and later stages of the plant pathogenesis response, putatively acting as both cellular signaling molecules and direct antipathogen agents. A single-cell assay, based on the fluorescent probe dichlorofluorescein, was used to scrutinize the generation and movement of ROS in tobacco epidermal tissue. ROS, generated within cells, quickly moved apoplastically as H2O2 into neighboring cells. Two classes of rapidly elicited intracellular ROS, originating from distinct sources, were distinguished. Cryptogein, the fungal elicitor from Phytophthora cryptogea, induced ROS from a flavin-containing oxidase source. ROS accumulation could be inhibited by a number of pharmacological agents, suggesting induction through an active signal transduction pathway. The insensitivity of the increase in ROS to the external addition of enzymes that dissipate ROS suggests that this oxidative increase is primarily intracellular. In contrast, amines and polyamines, compounds that form during wounding and pathogenesis, induced ROS at an apoplastic site from peroxidase- or amine oxidase-type enzyme(s). Salicylic acid, a putative inhibitor of cellular catalases and peroxidases, did not induce cellular ROS, as measured by dichlorofluorescein fluorescence. The physiological relevance of ROS-generated signals was indicated by the rapid alteration of the epidermal cell glutathione pool and the cellular redox state. In addition, induction of ROS by all elicitors was correlated with subsequent cell death. PMID:12237396

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

    PubMed

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

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

    PubMed Central

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

    2010-01-01

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

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

    SciTech Connect

    Perez-de-Arce, Karen; Foncea, Rocio . E-mail: rfoncea@med.puc.cl; Leighton, Federico

    2005-12-16

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

  11. Redox reactions in mammalian spermatogenesis and the potential targets of reactive oxygen species under oxidative stress

    PubMed Central

    Fujii, Junich