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Sample records for oxygen species involved

  1. Are Reactive Oxygen Species Involved in Microcystin-LR Intoxication?

    DTIC Science & Technology

    1988-05-12

    peroxidation in paracetamol intoxication, did not alter the effect of BHA pretreatment., -- 2-A 4" 4 2 - INTRODUCTION The toxic cyclic heptapeptide...changes, we hypothesized that compounds that alter the concentration N of reactive oxygen species would alter the toxic effects of the peptide...reactive oxygen species would alter the toxic effects of the peptide-hepatotoxin produced by Microcystis aeruginosa. We show here that pretreatment with a

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

    PubMed

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

    2005-09-01

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

  3. Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer.

    PubMed

    Hrycay, Eugene G; Bandiera, Stelvio M

    2015-01-01

    This review examines the involvement of cytochrome P450 (CYP) enzymes in the formation of reactive oxygen species in biological systems and discusses the possible involvement of reactive oxygen species and CYP enzymes in cancer. Reactive oxygen species are formed in biological systems as byproducts of the reduction of molecular oxygen and include the superoxide radical anion (∙O2-), hydrogen peroxide (H2O2), hydroxyl radical (∙OH), hydroperoxyl radical (HOO∙), singlet oxygen ((1)O2), and peroxyl radical (ROO∙). Two endogenous sources of reactive oxygen species are the mammalian CYP-dependent microsomal electron transport system and the mitochondrial electron transport chain. CYP enzymes catalyze the oxygenation of an organic substrate and the simultaneous reduction of molecular oxygen. If the transfer of oxygen to a substrate is not tightly controlled, uncoupling occurs and leads to the formation of reactive oxygen species. Reactive oxygen species are capable of causing oxidative damage to cellular membranes and macromolecules that can lead to the development of human diseases such as cancer. In normal cells, intracellular levels of reactive oxygen species are maintained in balance with intracellular biochemical antioxidants to prevent cellular damage. Oxidative stress occurs when this critical balance is disrupted. Topics covered in this review include the role of reactive oxygen species in intracellular cell signaling and the relationship between CYP enzymes and cancer. Outlines of CYP expression in neoplastic tissues, CYP enzyme polymorphism and cancer risk, CYP enzymes in cancer therapy and the metabolic activation of chemical procarcinogens by CYP enzymes are also provided.

  4. Prostaglandins and radical oxygen species are involved in microvascular effects of hyperoxia.

    PubMed

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

    2010-01-01

    Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging. Results were analysed using dose-response modelling. The response to ACh was reduced by 30% during oxygen breathing compared to air breathing [0.98 (0.81-1.15) PU vs. 1.45 (1.30-1.60) PU, p < 0.001]. ED(50) values were unchanged [2.25 (1.84-2.75) vs. 2.21 (1.79-2.74), not significant]. Aspirin pre-treatment abolished the difference in response between oxygen breathing and air breathing [maximum: 1.03 (0.90-1.16) vs. 0.89 (0.77-1.01), not significant; ED(50): 1.83 (1.46-2.30) vs. 1.95 (1.65-2.30), not significant]. ACh-mediated vasodilatation during 100% oxygen breathing was partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did not change the microvascular response to SNP [1.45 (1.28-1.62) vs. 1.40 (1.26-1.53), not significant]. These results favour the hypothesis that hyperoxic vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical oxygen species may be involved as vitamin C, independently of aspirin, partially restored ACh-mediated vasodilatation during hyperoxia.

  5. Involvement of Reactive Oxygen Species in the Action of Ciprofloxacin against Escherichia coli

    PubMed Central

    Goswami, M.; Mangoli, S. H.; Jawali, N.

    2006-01-01

    Ciprofloxacin is an important and commonly used member of the fluoroquinolone group of antibiotics. Ciprofloxacin inhibits DNA topoisomerase II and DNA topoisomerase IV activities, eventually leading to bacterial cell death. In addition, an increase of reactive oxygen species in the bacterial cells in response to ciprofloxacin has been shown. We investigated the role of reactive oxygen species in the antibacterial action of ciprofloxacin by studying the effects of different antioxidant compounds on ciprofloxacin susceptibility of Escherichia coli. Among the antioxidants checked, glutathione and ascorbic acid provided substantial protection against ciprofloxacin. The involvement of superoxide anion (O2−) and hydrogen peroxide (H2O2) in the antibacterial action of ciprofloxacin was analyzed using superoxide dismutase, catalase, and alkyl hydroperoxide reductase knockout strains of E. coli. The effects of multicopy sod genes on ciprofloxacin susceptibility of E. coli were also analyzed. On the basis of our results, we conclude that O2− and H2O2 may be involved in antibacterial action of ciprofloxacin. Our findings that glutathione gave protection against other fluoroquinolones and not against nonfluoroquinolone antibiotics imply that reactive oxygen species may have a similar role in the antibacterial action of all these fluoroquinolones and that glutathione-mediated protection is not a general phenomenon but specific to fluoroquinolones. These observations are of significance, as fluoroquinolones are important antibiotics with immense therapeutic value, and the effectiveness of treatment by these drugs may be affected by dietary intake and cellular levels of these antioxidants. PMID:16495256

  6. 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.

  7. Involvement of reactive oxygen species derived from mitochondria in neuronal injury elicited by methylmercury

    PubMed Central

    Ishihara, Yasuhiro; Tsuji, Mayumi; Kawamoto, Toshihiro; Yamazaki, Takeshi

    2016-01-01

    Methylmercury induces oxidative stress and subsequent neuronal injury. However, the mechanism by which methylmercury elicits reactive oxygen species (ROS) production remains under debate. In this study, we investigated the involvement of mitochondrial ROS in methylmercury-induced neuronal cell injury using human neuroblastoma SH-SY5Y-derived ρ0 cells, which have a deletion of mitochondrial DNA and thus decreased respiratory activity. SH-SY5Y cells were cultured for 60 days in the presence of ethidium bromide to produce ρ0 cells. Our ρ0 cells showed decreases in the cytochrome c oxidase expression and activity as well as oxygen consumption compared with original SH-SY5Y cells. Methylmercury at a concentration of 1 µM induced cell death with oxidative stress in original SH-SY5Y cells, but not ρ0 cells, indicating that ρ0 cells are resistant to methylmercury-induced oxidative stress. ρ0 cells also showed tolerance against hydrogen peroxide and superoxide anion, suggesting that ρ0 cells are resistant to total ROS. These data indicate that mitochondrial ROS are clearly involved in oxidative stress and subsequent cell death induced by methylmercury. Considering that the dominant mechanism of ROS generation elicited by methylmercury is due to direct antioxidant enzyme inhibition, mitochondria might play a role in amplifying ROS in methylmercury-induced neurotoxicity. PMID:27895385

  8. Involvement of reactive oxygen species and reactive nitrogen species in the wound response of Dasycladus vermicularis.

    PubMed

    Ross, Cliff; Küpper, Frithjof C; Jacobs, Robert S

    2006-04-01

    We investigated the signaling events involved in the wound response of the marine macroalga Dasycladus vermicularis, finding nitric oxide (NO) production in relation to injury. The addition of exogenous H2O2 to aliquots of injured algae accelerated the kinetics of NO production in the wounded region. Similarly, the addition of an NO donor caused an increase in detectable H2O2 around the site of injury. By wounding or incubating uninjured algae with an NO donor, peroxidase activity was enhanced. Based on the use of selected pharmacological probes, our results indicate that H2O2 production involves the upstream activation of signaling events similar to those observed in the physiology of higher plants.

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

    PubMed

    Gopalakrishnan, Anusha M; Kumar, Nirbhay

    2015-01-01

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

  10. 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.

  11. Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons.

    PubMed

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J

    2015-07-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of the three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguaiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons.

  12. Involvement of reactive oxygen species in lanthanum-induced inhibition of primary root growth.

    PubMed

    Liu, Yang-Yang; Wang, Ru-Ling; Zhang, Ping; Sun, Liang-Liang; Xu, Jin

    2016-11-01

    Although lanthanum (La) has been used as an agricultural plant growth stimulant for approximately 50 years, high concentrations are toxic to plants. Despite significant advances in recent years, the mechanisms underlying the effects of La on root system development remain unclear. Here, we report that a high concentration of La inhibits primary root (PR) elongation and induces lateral root (LR) development. La results in cell death in PR tips, thereby leading to the loss of meristematic cell division potential, stem cell niche activity, and auxin distribution in PR tips. Further analysis indicated that La induces reactive oxygen species (ROS) over-accumulation in PR tips. Reduction in ROS accumulation partially alleviated the inhibitory effects of La on PR elongation by improving cell survival in PR tips and thereby improving meristematic cell division potential and auxin distribution in PR tips. We also found ROS to be involved in La-induced endocytosis. Genetic analyses supported the described phenotype. Overall, our results indicate that La affects root growth, at least partially, by modulating ROS levels in roots to induce cell death in PR tips and subsequent auxin redistribution in roots, leading to remodeling of the root system architecture.

  13. 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

  14. Involvement of reactive oxygen species in lanthanum-induced inhibition of primary root growth

    PubMed Central

    Liu, Yang-Yang; Wang, Ru-Ling; Zhang, Ping; Sun, Liang-liang; Xu, Jin

    2016-01-01

    Although lanthanum (La) has been used as an agricultural plant growth stimulant for approximately 50 years, high concentrations are toxic to plants. Despite significant advances in recent years, the mechanisms underlying the effects of La on root system development remain unclear. Here, we report that a high concentration of La inhibits primary root (PR) elongation and induces lateral root (LR) development. La results in cell death in PR tips, thereby leading to the loss of meristematic cell division potential, stem cell niche activity, and auxin distribution in PR tips. Further analysis indicated that La induces reactive oxygen species (ROS) over-accumulation in PR tips. Reduction in ROS accumulation partially alleviated the inhibitory effects of La on PR elongation by improving cell survival in PR tips and thereby improving meristematic cell division potential and auxin distribution in PR tips. We also found ROS to be involved in La-induced endocytosis. Genetic analyses supported the described phenotype. Overall, our results indicate that La affects root growth, at least partially, by modulating ROS levels in roots to induce cell death in PR tips and subsequent auxin redistribution in roots, leading to remodeling of the root system architecture. PMID:27811082

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

    Treesearch

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

    2009-01-01

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

  16. Mining the enzymes involved in the detoxification of reactive oxygen species (ROS) in sugarcane.

    PubMed

    Kurama, Eiko E; Fenille, Roseli C; Rosa, Vicente E; Rosa, Daniel D; Ulian, Eugenio C

    2002-07-01

    Summary Adopting the sequencing of expressed sequence tags (ESTs) of a sugarcane database derived from libraries induced and not induced by pathogens, we identified EST clusters homologous to genes corresponding to enzymes involved in the detoxification of reactive oxygen species. The predicted amino acids of these enzymes are superoxide dismutases (SODs), glutathione-S-transferase (GST), glutathione peroxidase (GPX), and catalases. Three MnSOD mitochondrial precursors and 10 CuZnSOD were identified in sugarcane: the MnSOD mitochondrial precursor is 96% similar to the maize MnSOD mitochondrial precursor and, of the 10 CuZnSOD identified, seven were 98% identical to maize cytosolic CuZnSOD4 and one was 67% identical to putative peroxisomal CuZnSOD from Arabidopsis. Three homologues to class Phi GST were 87-88% identical to GST III from maize. Five GPX homologues were identified: three were homologous to cytosolic GPX from barley, one was 88% identical to phospholipid hydroperoxide glutathione peroxidase (PHGPX) from rice, and the last was 71% identical to GPX from A. thaliana. Three enzymes similar to maize catalase were identified in sugarcane: two were similar to catalase isozyme 3 and catalase chain 3 from maize, which are mitochondrial, and one was similar to catalase isozyme 1 from maize, whose location is peroxisomal subcellular. All enzymes were induced in all sugarcane libraries (flower, seed, root, callus, leaves) and also in the pathogen-induced libraries, except for CuZnSOD whose cDNA was detected in none of the libraries induced by pathogens (Acetobacter diazotroficans and Herbaspirillum rubrisubalbicans). The expression of the enzymes SOD, GST, GPX, and catalases involved in the detoxification was examined using reverse transcriptase-polymerase chain reaction in cDNA from leaves of sugarcane under biotic stress conditions, inoculated with Puccinia melanocephala, the causal agent of sugarcane rust disease.

  17. Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen species.

    PubMed

    Farhan, Mohd; Khan, Husain Yar; Oves, Mohammad; Al-Harrasi, Ahmed; Rehmani, Nida; Arif, Hussain; Hadi, Sheikh Mumtaz; Ahmad, Aamir

    2016-02-04

    Catechins, the dietary phytochemicals present in green tea and other beverages, are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. While it is believed that the antioxidant properties of catechins and related dietary agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, these properties cannot account for apoptosis induction and chemotherapeutic observations. Catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) are the four major constituents of green tea. In this article, using human peripheral lymphocytes and comet assay, we show that C, EC, EGC and EGCG cause cellular DNA breakage and can alternatively switch to a prooxidant action in the presence of transition metals such as copper. The cellular DNA breakage was found to be significantly enhanced in the presence of copper ions. Catechins were found to be effective in providing protection against oxidative stress induced by tertbutylhydroperoxide, as measured by oxidative DNA breakage in lymphocytes. The prooxidant action of catechins involved production of hydroxyl radicals through redox recycling of copper ions. We also determined that catechins, particularly EGCG, inhibit proliferation of breast cancer cell line MDA-MB-231 leading to a prooxidant cell death. Since it is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies, cancer cells would be more subject to redox cycling between copper ions and catechins to generate reactive oxygen species (ROS) responsible for DNA breakage. Such a copper dependent prooxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells.

  18. Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen Species

    PubMed Central

    Farhan, Mohd; Khan, Husain Yar; Oves, Mohammad; Al-Harrasi, Ahmed; Rehmani, Nida; Arif, Hussain; Hadi, Sheikh Mumtaz; Ahmad, Aamir

    2016-01-01

    Catechins, the dietary phytochemicals present in green tea and other beverages, are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. While it is believed that the antioxidant properties of catechins and related dietary agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, these properties cannot account for apoptosis induction and chemotherapeutic observations. Catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) are the four major constituents of green tea. In this article, using human peripheral lymphocytes and comet assay, we show that C, EC, EGC and EGCG cause cellular DNA breakage and can alternatively switch to a prooxidant action in the presence of transition metals such as copper. The cellular DNA breakage was found to be significantly enhanced in the presence of copper ions. Catechins were found to be effective in providing protection against oxidative stress induced by tertbutylhydroperoxide, as measured by oxidative DNA breakage in lymphocytes. The prooxidant action of catechins involved production of hydroxyl radicals through redox recycling of copper ions. We also determined that catechins, particularly EGCG, inhibit proliferation of breast cancer cell line MDA-MB-231 leading to a prooxidant cell death. Since it is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies, cancer cells would be more subject to redox cycling between copper ions and catechins to generate reactive oxygen species (ROS) responsible for DNA breakage. Such a copper dependent prooxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells. PMID:26861392

  19. Hypoxic relaxation of penile arteries: involvement of endothelial nitric oxide and modulation by reactive oxygen species

    PubMed Central

    Kaminski, Pawel M.; Bagi, Zsolt; Ahmad, Mansoor; Wolin, Michael S.

    2010-01-01

    Although obesity-related cardiovascular disease and hypoxia are associated with erectile dysfunction, little is known about the direct effects of hypoxia on penile arteries. In the present study, the effects of acute hypoxia (Po2 = ∼10 Torr, 20 min) were investigated in isolated penile arteries to determine the influence of endothelium removal, nitric oxide (NO) synthase (NOS), cyclooxygenase (COX), NADPH oxidase, changes in reactive oxygen species (ROS), and a high-fat diet. Hypoxia-relaxed penile arteries contracted with phenylephrine by ∼50%. Relaxation to hypoxia and acetylcholine was reduced by endothelium removal and by inhibition of NOS (Nω-nitro-l-arginine) and COX (indomethacin) but was enhanced by Tempol and by NADPH oxidase inhibition with apocynin and gp91ds-tat. Basal superoxide levels detected by lucigenin chemiluminescence were reduced by Tempol and gp91ds-tat and were enhanced by NOS blockade. Hypoxic relaxant responses were enhanced by catalase and ebselen. Exogenous peroxide evoked relaxations of penile arteries, which were partially inhibited by endothelium removal and by the inhibition of COX and extracellular signal-regulated mitogen-activated protein kinase (MAPK) but enhanced by p38 MAPK blockade. The NO-dependent component of relaxation to hypoxia was impaired in penile arteries from high-fat diet-fed, obese rats associated with increased superoxide production. Thus hypoxic relaxation of penile arteries is partially mediated by endothelial NO in a manner that is normally attenuated by endogenous ROS production. Obesity further increases superoxide production and impairs the influence of NO. Therefore, cardiovascular disease involving decreased NO bioavailability and/or enhanced ROS generation may contribute to erectile dysfunction through impairing the relaxation of penile arteries to hypoxia. PMID:20581086

  20. 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.

  1. The involvement of reactive oxygen species in hypoxic injury to rat liver.

    PubMed

    Younes, M; Strubelt, O

    1988-03-01

    Isolated perfused livers from fasted, but not from fed rats showed hepatotoxic responses when subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Toxicity was evident by a release of glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. This indicates, that the liver is resistant to hypoxic injury as long as glycogen is present to maintain anaerobic ATP-synthesis. This is substantiated by the fact that addition of fructose--but not glucose--to the medium resulted in a protection of the liver against hypoxic injury concomitant with its degradation to lactate + pyruvate. Superoxide dismutase, catalase, desferrioxamine and allopurinol prevented hypoxic liver injury suggesting a substantial role of reactive oxygen species formed via the xanthine oxidase reaction in mediating hypoxic liver injury.

  2. Mitochondrial dysfunction in rat brain with aging Involvement of complex I, reactive oxygen species and cardiolipin.

    PubMed

    Petrosillo, G; Matera, M; Casanova, G; Ruggiero, F M; Paradies, G

    2008-11-01

    Reactive oxygen species (ROS) are considered a key factor in brain aging process. Mitochondrial respiration is an important site of ROS production and hence a potential contributor to brain functional changes with aging. In this study we examined the effect of aging on complex I activity, oxygen consumption, ROS production and phospholipid composition in rat brain mitochondria. The activity of complex I was reduced by 30% in brain mitochondria from 24 months aged rats relative to young animals. These changes in complex I activity were associated with parallel changes in state 3 respiration. H(2)O(2) generation was significantly increased in mitochondria isolated from aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, decreased by 31% as function of aging, while there was a significant increase in the level of peroxidized cardiolipin. The age-related decrease in complex I activity in brain mitochondria could be reversed by exogenously added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids. It is proposed that aging causes brain mitochondrial complex I dysfunction which can be attributed to ROS-induced cardiolipin oxidation. These findings may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with brain aging.

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

    PubMed

    Taheri, Parissa; Kakooee, Tahereh

    2017-09-01

    Alternaria blight is a major and destructive disease of potato worldwide. In recent years, A. tenuissima is recognized as the most prevalent species of this phytopathogenic fungus in potato fields of Asian countries, which causes high yield losses every year. Any potato cultivar with complete resistance to this disease is not recognized, so far. Therefore, screening resistance levels of potatoes and identification of plant defense mechanisms against this fungus might be important for designing novel and effective disease management strategies for controlling the disease. In this research, the role of reactive oxygen species, antioxidants, lignin and phenolics in potato basal resistance to A. tenuissima was compared in the partially resistant Ramus and susceptible Bamba cultivars. Priming O2(-) and H2O2 production and enhanced activity of peroxidase (POX) and catalase (CAT) during interaction with A. tenuissima were observed in Ramus cultivar. Application of ROS generating systems and scavengers revealed critical role of O2(-) and H2O2 in potato defense, which was associated with lignification and phenolics production. More OH(-) and lipid peroxidation in the susceptible Bamba compared to Ramus cultivar showed their negative effects on resistance. Priming the POX and CAT activity, in correlation with upregulation of the corresponding genes was observed in Ramus. The POX and CAT inhibitors increased disease progress, which was related with decreased lignification. This assay demonstrated not only POX-dependency of lignification, but also its dependence on CAT. However, POX had more importance than CAT in potato defense and in lignification. These findings highlight the function of ROS accumulation and homeostasis in potato resistance against A. tenuissima. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Involvement of reactive oxygen species in cocaine-taking behaviors in rats.

    PubMed

    Jang, Eun Young; Ryu, Yeon-Hee; Lee, Bong Hyo; Chang, Su-Chan; Yeo, Mi Jin; Kim, Sang Hyun; Folsom, Ryan J; Schilaty, Nathan D; Kim, Kwang Joong; Yang, Chae Ha; Steffensen, Scott C; Kim, Hee Young

    2015-07-01

    Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-administration behavior, cocaine-induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), either pre- or post-treatment, significantly decreased cocaine self-administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self-administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self-administering cocaine. TEMPOL significantly attenuated cocaine-induced enhancement of DA release in the NAc, compared to saline controls. TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine. © 2014 Society for the Study of Addiction.

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

    PubMed

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

    2004-10-15

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

  6. Peroxiredoxin-3 Is Involved in Bactericidal Activity through the Regulation of Mitochondrial Reactive Oxygen Species

    PubMed Central

    Lee, Sena; Wi, Sae Mi; Min, Yoon

    2016-01-01

    Peroxiredoxin-3 (Prdx3) is a mitochondrial protein of the thioredoxin family of antioxidant peroxidases and is the principal peroxidase responsible for metabolizing mitochondrial hydrogen peroxide. Recent reports have shown that mitochondrial reactive oxygen species (mROS) contribute to macrophage-mediated bactericidal activity in response to Toll-like receptors. Herein, we investigated the functional effect of Prdx3 in bactericidal activity. The mitochondrial localization of Prdx3 in HEK293T cells was confirmed by cell fractionation and confocal microscopy analyses. To investigate the functional role of Prdx3 in bactericidal activity, Prdx3-knockdown (Prdx3KD) THP-1 cells were generated. The mROS levels in Prdx3KD THP-1 cells were significantly higher than those in control THP-1 cells. Moreover, the mROS levels were markedly increased in response to lipopolysaccharide. Notably, the Salmonella enterica serovar Typhimurium infection assay revealed that the Prdx3KD THP-1 cells were significantly resistant to S. Typhimurium infection, as compared with control THP-1 cells. Taken together, these results indicate that Prdx3 is functionally important in bactericidal activity through the regulation of mROS. PMID:28035213

  7. Cardiac melanocytes influence atrial reactive oxygen species involved with electrical and structural remodeling in mice

    PubMed Central

    Hwang, Hayoung; Liu, Fang; Petrenko, Nataliya B; Huang, Jianhe; Schillinger, Kurt J; Patel, Vickas V

    2015-01-01

    Cardiac melanocyte-like cells (CMLCs) contribute to atrial arrhythmias when missing the melanin synthesis enzyme dopachrome tautomerase (Dct). While scavenging reactive oxygen species (ROS) in Dct-null mice partially suppressed atrial arrhythmias, it remains unclear if CMLCs influence atrial ROS and structure or if the electrical response of CMLCs to ROS differs from that of atrial myocytes. This study is designed to determine if CMLCs contribute to overall atrial oxidative stress or structural remodeling, and if ROS affects the electrophysiology of CMLCs differently than atrial myocytes. Immunohistochemical analysis showed higher expression of the oxidative marker 8-hydroxy-2′-deoxyguanosine in Dct-null atria versus Dct-heterozygous (Dct-het) atria. Exposing isolated CMLCs from Dct-het and Dct-null mice to hydrogen peroxide increased superoxide anion more in Dct-null CMLCs. Trichrome staining showed increased fibrosis in Dct-null atria, and treating Dct-null mice with the ROS scavenger Tempol reduced atrial fibrosis. Action potential recordings from atrial myocytes and isolated Dct-het and Dct-null CMLCs in response to hydrogen peroxide showed that the EC50 for action potential duration (APD) prolongation of Dct-null CMLCs was 8.2 ± 1.7 μmol/L versus 16.8 ± 2.0 μmol/L for Dct-het CMLCs, 19.9 ± 2.1 μmol/L for Dct-null atrial myocytes, and 20.5 ± 1.9 μmol/L for Dct-het atrial myocytes. However, APD90 was longer in CMLCs versus atrial myocytes in response to hydrogen peroxide. Hydrogen peroxide also induced more afterdepolarizations in CMLCs compared to atrial myocytes. These studies suggest that Dct within CMLCs contributes to atrial ROS balance and remodeling. ROS prolongs APD to a greater extent and induces afterdepolarizations more frequently in CMLCs than in atrial myocytes. PMID:26400986

  8. AMPK is involved in mediation of erythropoietin influence on metabolic activity and reactive oxygen species production in white adipocytes.

    PubMed

    Wang, Li; Di, Lijun; Noguchi, Constance Tom

    2014-09-01

    Erythropoietin, discovered for its indispensable role during erythropoiesis, has been used in therapy for selected red blood cell disorders in erythropoietin-deficient patients. The biological activities of erythropoietin have been found in animal models to extend to non-erythroid tissues due to the expression of erythropoietin receptor. We previously demonstrated that erythropoietin promotes metabolic activity and white adipocytes browning to increase mitochondrial function and energy expenditure via peroxisome proliferator-activated receptor alpha and Sirtuin1. Here we report that AMP-activated protein kinase was activated by erythropoietin possibly via Ca(2+)/calmodulin-dependent protein kinase kinase in adipocytes as well as in white adipose tissue from diet induced obese mice. Erythropoietin increased cellular nicotinamide adenine dinucleotide via increased AMP-activated protein kinase activity, possibly leading to Sirtuin1 activation. AMP-activated protein kinase knock down reduced erythropoietin mediated increase in cellular oxidative function including the increased oxygen consumption rate, fatty acid utilization and induction of key metabolic genes. Under hypoxia, adipocytes were found to generate more reactive oxygen species, and erythropoietin reduced the reactive oxygen species and increased antioxidant gene expression, suggesting that erythropoietin may provide protection from oxidative stress in adipocytes. Erythropoietin also reversed increased nicotinamide adenine dinucleotide by hypoxia via increased AMP-activated protein kinase. Additionally, AMP-activated protein kinase is found to be involved in erythropoietin stimulated increase in oxygen consumption rate, fatty acid oxidation and mitochondrial gene expression. AMP-activated protein kinase knock down impaired erythropoietin stimulated increases in antioxidant gene expression. Collectively, our findings identify the AMP-activated protein kinase involvement in erythropoietin signaling in

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

    PubMed Central

    Yamauchi, Takaki

    2014-01-01

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

  10. PKD1 Protein Is Involved in Reactive Oxygen Species-mediated Mitochondrial Depolarization in Cooperation with Protein Kinase Cδ (PKCδ)*

    PubMed Central

    Zhang, Thianzhou; Sell, Philip; Braun, Ursula; Leitges, Michael

    2015-01-01

    In this study, we used gene targeting in mice to identify the in vivo functions of PKD1. In addition to phenotypically characterizing the resulting knock-out animals, we also used mouse embryonic fibroblasts to investigate the associated signaling pathways in detail. This study is the first to use genetic deletion to reveal that PKD1 is a key regulator involved in determining the threshold of mitochondrial depolarization that leads to the production of reactive oxygen species. In addition, we also provide clear evidence that PKCδ is upstream of PKD1 in this process and acts as the activating kinase of PKD1. Therefore, our in vivo data indicate that PKD1 functions not only in the context of aging but also during nutrient deprivation, which occurs during specific phases of tumor growth. PMID:25759386

  11. Reactive Oxygen Species Are Involved in Brassinosteroid-Induced Stress Tolerance in Cucumber1[W

    PubMed Central

    Xia, Xiao-Jian; Wang, Yan-Jie; Zhou, Yan-Hong; Tao, Yuan; Mao, Wei-Hua; Shi, Kai; Asami, Tadao; Chen, Zhixiang; Yu, Jing-Quan

    2009-01-01

    Brassinosteroids (BRs) induce plant tolerance to a wide spectrum of stresses. To study how BR induces stress tolerance, we manipulated the BR levels in cucumber (Cucumis sativus) through a chemical genetics approach and found that BR levels were positively correlated with the tolerance to photo-oxidative and cold stresses and resistance to Cucumber mosaic virus. We also showed that BR treatment enhanced NADPH oxidase activity and elevated H2O2 levels in apoplast. H2O2 levels were elevated as early as 3 h and returned to basal levels 3 d after BR treatment. BR-induced H2O2 accumulation was accompanied by increased tolerance to oxidative stress. Inhibition of NADPH oxidase and chemical scavenging of H2O2 reduced BR-induced oxidative and cold tolerance and defense gene expression. BR treatment induced expression of both regulatory genes, such as RBOH, MAPK1, and MAPK3, and genes involved in defense and antioxidant responses. These results strongly suggest that elevated H2O2 levels resulting from enhanced NADPH oxidase activity are involved in the BR-induced stress tolerance. PMID:19386805

  12. Calcium-dependent trichosanthin-induced generation of reactive oxygen species involved in apoptosis of human choriocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, Chunyang; Ma, Hui; Chen, Die Yan

    2001-04-01

    The type-I ribosome-inactivating protein trichosanthin (TCS) has a broad spectrum of biological and pharmacological activities, including abortifacient, anti-tumor and anti-HIV. We found for the first time that TCS induced production of reactive oxygen species (ROS) in JAR cells by using fluorescent probe 2',7'-dichlorofluorescin diacetate with confocal laser scanning microscopy. TCS-induced ROS showed dependence on the increase in intracellular calcium and on the presence of extracellular calcium. The production of ROS increased rapidly after the application of TCS, which paralleled TCS-indued increase in intracellular calcium monitored using fluo 3-AM, suggesting that TCS-induced ROS might mediate by the increase in intracellular Ca2PLU concentration. Simultaneous observation of the nuclear morphological changes and production of ROS in JAR cells with two-photon laser scanning microscopy and confocal laser scanning microscopy revealed that ROS involved in the apoptosis of JAR cells, which was confirmed by that antioxidant (alpha) -tocopherol prevented TCS-induced ROS formation and cell death. The finding that calcium-dependent TCS-induced ROS involved in the apoptosis of JAR cells might provide new insight into the anti-tumor and anti-HIV mechanism of TCS.

  13. The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: involvement of the Nrf2-ARE signaling pathway.

    PubMed

    Saw, Constance Lay Lay; Guo, Yue; Yang, Anne Yuqing; Paredes-Gonzalez, Ximena; Ramirez, Christina; Pung, Douglas; Kong, Ah-Ng Tony

    2014-10-01

    Quercetin, kaempferol, and pterostilbene are abundant in berries. The anti-oxidative properties of these constituents may contribute to cancer chemoprevention. However, their precise mechanisms of action and their combinatorial effects are not completely understood. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates anti-oxidative stress enzymes and Phase II drug metabolizing/detoxifying enzymes by binding to antioxidant response element (ARE). This study aimed to investigate the anti-oxidative stress activities of quercetin, kaempferol, and pterostilbene individually and in combination, as well as the involvement of the Nrf2-ARE signaling pathway. Quercetin, kaempferol, and pterostilbene all exhibited strong free-radical scavenging activity in the DPPH assay. The MTS assay revealed that low concentration combinations we tested were relatively non-toxic to HepG2-C8 cells. The results of the DCFH-DA assay and combination index (CI) indicated that quercetin, kaempferol, and pterostilbene attenuated intracellular reactive oxygen species (ROS) levels when pretreated individually and had synergistic effects when used in combination. In addition, the combination treatment significantly induced ARE and increased the mRNA and protein expression of Nrf2-regulated genes. Collectively, our study demonstrated that the berry constituents quercetin, kaempferol, and pterostilbene activated the Nrf2-ARE signaling pathway and exhibited synergistic anti-oxidative stress activity at appropriate concentrations.

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

    PubMed

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

    2012-03-01

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

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

    PubMed Central

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

    2012-01-01

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

  16. Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication.

    PubMed

    Cavalheiro, Mariana G; Costa, Leandro Silva DA; Campos, Holmes S; Alves, Letícia S; Assunção-Miranda, Iranaia; Poian, Andrea T DA

    2016-09-01

    Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection.

  17. Cytotoxic responses to 405nm light exposure in mammalian and bacterial cells: Involvement of reactive oxygen species.

    PubMed

    Ramakrishnan, Praveen; Maclean, Michelle; MacGregor, Scott J; Anderson, John G; Grant, M Helen

    2016-06-01

    Light at wavelength 405 nm is an effective bactericide. Previous studies showed that exposing mammalian cells to 405 nm light at 36 J/cm(2) (a bactericidal dose) had no significant effect on normal cell function, although at higher doses (54 J/cm(2)), mammalian cell death became evident. This research demonstrates that mammalian and bacterial cell toxicity induced by 405 nm light exposure is accompanied by reactive oxygen species production, as detected by generation of fluorescence from 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate. As indicators of the resulting oxidative stress in mammalian cells, a decrease in intracellular reduced glutathione content and a corresponding increase in the efflux of oxidised glutathione were observed from 405 nm light treated cells. The mammalian cells were significantly protected from dying at 54 J/cm(2) in the presence of catalase, which detoxifies H2O2. Bacterial cells were significantly protected by sodium pyruvate (H2O2 scavenger) and by a combination of free radical scavengers (sodium pyruvate, dimethyl thiourea (OH scavenger) and catalase) at 162 and 324 J/cm(2). Results therefore suggested that the cytotoxic mechanism of 405 nm light in mammalian cells and bacteria could be oxidative stress involving predominantly H2O2 generation, with other ROS contributing to the damage.

  18. Heat shock induces apoptosis through reactive oxygen species involving mitochondrial and death receptor pathways in corneal cells.

    PubMed

    Hsu, Ya-Ling; Yu, Hsin-Su; Lin, Hsien-Chung; Wu, Kwou-Yeung; Yang, Rei-Cheng; Kuo, Po-Lin

    2011-10-01

    Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of infrared radiation on ocular disease. In addition to photons, heat is generated as a consequence of infrared irradiation, and heat shock is widely considered to be an environmental stressor. Here, we are the first to investigate the biological effect of heat shock on Statens Seruminstitut Rabbit Cornea (SIRC) cells. Our results indicate that heat shock exhibits effective cell proliferation inhibition by inducing apoptosis. Heat shock triggers the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in caspase-9 activity. In addition, heat shock triggered the death receptor apoptotic pathway indicated by a change in Fas ligand expression, resulting in caspase-8 activity. Furthermore, we also found that generation of reactive oxygen species (ROS) is a critical mediator in heat shock-induced apoptosis. In addition, the antioxidant vitamin C significantly decreased heat shock-mediated apoptosis. Taken together, these findings suggest a critical role for ROS involving mitochondrial and death receptor pathways in heat shock-mediated apoptosis of cornea cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Reactive oxygen species and calcium signals in skeletal muscle: A crosstalk involved in both normal signaling and disease.

    PubMed

    Espinosa, Alejandra; Henríquez-Olguín, Carlos; Jaimovich, Enrique

    2016-09-01

    Reactive Oxygen Species (ROS) have been profusely studied as agents of potential damage to living cells and they have been related to a number of pathological processes. Increasing evidence points to a more positive role of ROS in cell signaling and the detailed mechanism that regulates the precise amount of ROS needed for cell functioning without the deleterious effects of excess ROS still needs to be resolved in detail. In skeletal muscle the main source of ROS during normal functioning appears to be NADPH oxidase 2 (NOX2), which is activated by electrical stimuli (or exercise) through a cascade of events that include ATP release through pannexin1 channels. NOX2 is a protein complex that assembles in the T-tubule membrane before activation and ROS production by NOX2 appears to be important for muscle adaptation through gene expression and mitochondrial biogenesis as well as for improving glucose transport after insulin action. Excess ROS production (or diminished antioxidant defenses) plays a role in a number of pathological processes in skeletal muscle. Together with increased reactive nitrogen species, an increase in ROS appears to have a deleterious role in a model of Duchenne muscular dystrophy as well as muscle wasting in other diseases such as aging sarcopenia and cancer cachexia. In addition, ROS is involved in obesity and muscle insulin resistance, both of which are causally related to type 2 diabetes. A detailed description of the fine-tuning of ROS (including all sources of ROS) in skeletal muscle in health and disease will significantly contribute to our knowledge of both muscle adaptation and muscle related pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-07-01

    Endosperm cap (CAP) weakening and embryo elongation growth are prerequisites for the completion of lettuce seed germination. Although it has been proposed that the cell wall loosening underlying these processes results from an enzymatic mechanism, it is still unclear which enzymes are involved. Here it is shown that reactive oxygen species (ROS), which are non-enzymatic factors, may be involved in the two processes. In Guasihong lettuce seeds imbibed in water, O2·(-) and H2O2 accumulated and peroxidase activity increased in the CAP, whereas its puncture force decreased. In addition, in the radicle, the increase in embryo growth potential was accompanied by accumulation of O2·(-) and an increase in peroxidase activity. Imbibing seeds in 0.3% sodium dichloroisocyanurate (SDIC) reduced endosperm viability and the levels of O2·(-), H2O2, and peroxidase activity in the CAP, whereas the decrease in its puncture force was inhibited. However, in the embryo, SDIC did not affect the accumulation of O2·(-), peroxidase activity, and the embryo growth potential. As a result, SDIC caused atypical germination, in which the endosperm ruptured at the boundary between the CAP and lateral endosperm. ROS scavengers and ROS generation inhibitors inhibited the CAP weakening and also decreased the embryo growth potential, thus decreasing the percentage of seed germination. Exogenous ROS and ROS generation inducers increased the percentage of CAP rupture to some extent, and the addition of H2O2 to 0.3% SDIC enabled some seeds to undergo typical germination. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

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

    PubMed Central

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

    2014-01-01

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

  2. Differential involvement of reactive oxygen species in apoptosis induced by two classes of selenium compounds in human prostate cancer cells.

    PubMed

    Li, Guang-Xun; Hu, Hongbo; Jiang, Cheng; Schuster, Todd; Lü, Junxuan

    2007-05-01

    Selenium is a promising chemopreventive agent for prostate cancer, possibly via an induction of apoptosis. Earlier studies have shown that selenite induces DNA single strand breaks (SSBs), reactive oxygen species (ROS), p53 Ser-15 phosphorylation and caspase-dependent and -independent apoptosis, whereas a methylselenol precursor methylseleninic acid (MSeA) induces caspase-mediated apoptosis regardless of p53 status. Here we address three main questions: What types of ROS are induced by selenite vs. MSeA in LNCaP (p53 wild type, androgen-responsive) and DU145 (mutant p53, androgen-independent) prostate cancer cells? Does ROS generation depend on androgen signaling? What are the relationships among ROS, DNA SSBs, p53 and caspases? We show that selenite (5 microM) induced superoxide and hydrogen peroxide in LNCaP cells much more than in DU145 cells and the ROS generation was not affected by physiological androgen stimulation. MSeA (10 microM) induced apoptosis without either type of ROS in both cell lines. In LNCaP cells, we established superoxide as a primary mediator for selenite-induced DNA SSBs, p53 activation and caspase-mediated apoptosis. Furthermore a p53-dominant negative mutant attenuated selenite-induced ROS, leading to a proportionate protection against apoptosis. The results support the p53-mitochondria axis in a feedback loop for sustaining superoxide production to lead to efficient caspase-mediated apoptosis by selenite. In contrast, caspase-mediated apoptosis induced by MSeA does not involve ROS induction. Since p53 is frequently mutated or deleted in prostate cancer and many other cancers, our results suggest that genotoxic vs. nongenotoxic classes of selenium may exert differential apoptosis efficacy depending on the p53 status of the cancer cells. (c) 2007 Wiley-Liss, Inc.

  3. TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO.

    PubMed

    Aubdool, Aisah A; Kodji, Xenia; Abdul-Kader, Nayaab; Heads, Richard; Fernandes, Elizabeth S; Bevan, Stuart; Brain, Susan D

    2016-08-01

    Transient receptor potential ankyrin-1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1-mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde. Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry. Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild-type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde-induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS-derived NO pathways. Cinnamaldehyde-mediated vasodilatation was significantly reduced by treatment with reactive oxygen nitrogen species (RONS) scavenger such as catalase and the SOD mimetic TEMPOL, supporting a role of RONS in the downstream vasodilator TRPA1-mediated response. Co-treatment with a non-selective NOS inhibitor L-NAME and antioxidant apocynin further inhibited the TRPA1-mediated vasodilatation. Cinnamaldehyde treatment induced the generation of peroxynitrite that was blocked by the peroxynitrite scavenger FeTPPS and shown to be dependent on TRPA1, as reflected by an increase in protein tyrosine nitration in the skin of WT, but not in TRPA1 KO mice. This study provides in vivo evidence that TRPA1-induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS-derived NO, in addition to the traditional neuropeptide component. A novel role of peroxynitrite is revealed, which is generated downstream of TRPA1 activation by cinnamaldehyde. This mechanistic pathway underlying TRPA1-mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations. © 2016 The Authors British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  4. TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO

    PubMed Central

    Aubdool, Aisah A; Kodji, Xenia; Abdul‐Kader, Nayaab; Heads, Richard; Fernandes, Elizabeth S; Bevan, Stuart

    2016-01-01

    Abstract Background and Purpose Transient receptor potential ankyrin‐1 (TRPA1) activation is known to mediate neurogenic vasodilatation. We investigated the mechanisms involved in TRPA1‐mediated peripheral vasodilatation in vivo using the TRPA1 agonist cinnamaldehyde. Experimental Approach Changes in vascular ear blood flow were measured in anaesthetized mice using laser Doppler flowmetry. Key Results Topical application of cinnamaldehyde to the mouse ear caused a significant increase in blood flow in the skin of anaesthetized wild‐type (WT) mice but not in TRPA1 knockout (KO) mice. Cinnamaldehyde‐induced vasodilatation was inhibited by the pharmacological blockade of the potent microvascular vasodilator neuropeptide CGRP and neuronal NOS‐derived NO pathways. Cinnamaldehyde‐mediated vasodilatation was significantly reduced by treatment with reactive oxygen nitrogen species (RONS) scavenger such as catalase and the SOD mimetic TEMPOL, supporting a role of RONS in the downstream vasodilator TRPA1‐mediated response. Co‐treatment with a non‐selective NOS inhibitor L‐NAME and antioxidant apocynin further inhibited the TRPA1‐mediated vasodilatation. Cinnamaldehyde treatment induced the generation of peroxynitrite that was blocked by the peroxynitrite scavenger FeTPPS and shown to be dependent on TRPA1, as reflected by an increase in protein tyrosine nitration in the skin of WT, but not in TRPA1 KO mice. Conclusion and Implications This study provides in vivo evidence that TRPA1‐induced vasodilatation mediated by cinnamaldehyde requires neuronal NOS‐derived NO, in addition to the traditional neuropeptide component. A novel role of peroxynitrite is revealed, which is generated downstream of TRPA1 activation by cinnamaldehyde. This mechanistic pathway underlying TRPA1‐mediated vasodilatation may be important in understanding the role of TRPA1 in pathophysiological situations. PMID:27189253

  5. Reactive Oxygen Species Are Involved in Gibberellin/Abscisic Acid Signaling in Barley Aleurone Cells1[C][W][OA

    PubMed Central

    Ishibashi, Yushi; Tawaratsumida, Tomoya; Kondo, Koji; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Zheng, Shao-Hui; Yuasa, Takashi; Iwaya-Inoue, Mari

    2012-01-01

    Reactive oxygen species (ROS) act as signal molecules for a variety of processes in plants. However, many questions about the roles of ROS in plants remain to be clarified. Here, we report the role of ROS in gibberellin (GA) and abscisic acid (ABA) signaling in barley (Hordeum vulgare) aleurone cells. The production of hydrogen peroxide (H2O2), a type of ROS, was induced by GA in aleurone cells but suppressed by ABA. Furthermore, exogenous H2O2 appeared to promote the induction of α-amylases by GA. In contrast, antioxidants suppressed the induction of α-amylases. Therefore, H2O2 seems to function in GA and ABA signaling, and in regulation of α-amylase production, in aleurone cells. To identify the target of H2O2 in GA and ABA signaling, we analyzed the interrelationships between H2O2 and DELLA proteins Slender1 (SLN1), GA-regulated Myb transcription factor (GAmyb), and ABA-responsive protein kinase (PKABA) and their roles in GA and ABA signaling in aleurone cells. In the presence of GA, exogenous H2O2 had little effect on the degradation of SLN1, the primary transcriptional repressor mediating GA signaling, but it promoted the production of the mRNA encoding GAMyb, which acts downstream of SLN1 and involves induction of α-amylase mRNA. Additionally, H2O2 suppressed the production of PKABA mRNA, which is induced by ABA:PKABA represses the production of GAMyb mRNA. From these observations, we concluded that H2O2 released the repression of GAMyb mRNA by PKABA and consequently promoted the production of α-amylase mRNA, thus suggesting that the H2O2 generated by GA in aleurone cells is a signal molecule that antagonizes ABA signaling. PMID:22291200

  6. Age dependence of the level of the enzymes involved in the protection against active oxygen species in the rat brain

    SciTech Connect

    Scarpa, M.; Rigo, A.; Viglino, P.; Stevanato, R.; Bracco, F.; Battistin, L.

    1987-06-01

    Levels of Cu, Zn superoxide dismutase (CuSOD), Mn superoxide dismutase (MnSOD), catalase, and glutathione peroxidase (GPx) were assessed in the rat brain cortex. The concentrations of Cu- and MnSOD were found to increase linearly with the logarithm of the age of the animal from 3 days before birth to 30 months, both in the whole cortex tissue and in its cytoplasmic fraction. Catalase and GPx levels showed different trends; in particular, GPx, which appears to play a key role in detoxification of hydrogen peroxide, after an initial fall increases steadily with age. The enhancement of the levels of SOD and GPx could be related to protection against an increased production of reactive oxygen species in the aging process.

  7. Involvement of oxidative stress response genes in redox homeostasis, the level of reactive oxygen species, and ageing in Saccharomyces cerevisiae.

    PubMed

    Drakulic, Tamara; Temple, Mark D; Guido, Ron; Jarolim, Stefanie; Breitenbach, Michael; Attfield, Paul V; Dawes, Ian W

    2005-12-01

    Saccharomyces cerevisiae mutants lacking oxidative stress response genes were used to investigate which genes are required under normal aerobic conditions to maintain cellular redox homeostasis, using intracellular glutathione redox potential (glutathione E(h)) to indicate the redox environment of the cells. Levels of reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) were also assessed by FACS using dihydroethidium and rhodamine 123 as fluorescent probes. Cells became more oxidised as strains shifted from exponential growth to stationary phase. During both phases the presence of reduced thioredoxin and the activity of glutathione reductase were important for redox homeostasis. Thioredoxin reductase contributed less during exponential phase when there was a strong requirement for active Yap1p transcription factor, but was critical during stationary phase. The absence of ROS detoxification systems, such as catalases or superoxide dismutases, had a lesser effect on glutathione E(h), but a more pronounced effect on ROS levels and MMP. These results reflect the major shift in ROS generation as cells switch from fermentative to respiratory metabolism and also showed that there was not a strong correlation between ROS production, MMP and cellular redox environment. Heterogeneity was detected in populations of strains with compromised anti-oxidant defences, and as cells aged they shifted from one cell type with low ROS content to another with much higher intracellular ROS.

  8. Involvement of Reactive Oxygen Species and Mitochondrial Proteins in Biophoton Emission in Roots of Soybean Plants under Flooding Stress.

    PubMed

    Kamal, Abu Hena Mostafa; Komatsu, Setsuko

    2015-05-01

    To understand the mechanism of biophoton emission, ROS and mitochondrial proteins were analyzed in soybean plants under flooding stress. Enzyme activity and biophoton emission were increased in the flooding stress samples when assayed in reaction mixes specific for antioxidant enzymes and reactive oxygen species; although the level of the hydroxyl radicals was increased at day 4 (2 days of flooding) compared to nonflooding at day 4, the emission of biophotons did not change. Mitochondria were isolated and purified from the roots of soybean plants grown under flooding stress by using a Percoll gradient, and proteins were analyzed by a gel-free proteomic technique. Out of the 98 mitochondrial proteins that significantly changed abundance under flooding stress, 47 increased and 51 decreased at day 4. The mitochondrial enzymes fumarase, glutathione-S-transferase, and aldehyde dehydrogenase increased at day 4 in protein abundance and enzyme activity. Enzyme activity and biophoton emission decreased at day 4 by the assay of lipoxygenase under stress. Aconitase, acyl CoA oxidase, succinate dehydrogenase, and NADH ubiquinone dehydrogenase were up-regulated at the transcription level. These results indicate that oxidation and peroxide scavenging might lead to biophoton emission and oxidative damage in the roots of soybean plants under flooding stress.

  9. Cholesterol secoaldehyde induces apoptosis in J774 macrophages via mitochondrial pathway but not involving reactive oxygen species as mediators.

    PubMed

    Gao, Xueli; Raghavamenon, Achuthan C; D'Auvergne, Oswald; Uppu, Rao M

    2009-11-13

    Cholesterol secoaldehyde (3beta-hydroxy-5-oxo-5,6-secocholestan-6-al or ChSeco) is an oxysterol known to be formed in reactions of ozone with cholesterol and also when cholesterol-5alpha-hydroperoxide undergoes Hock cleavage. In view of its widespread occurrence and atherogenic potential, we examined the effects of ChSeco on mouse J774 macrophage viability and events associated with apoptosis. A dose-dependent decrease in cell viability, disruptions in mitochondrial transmembrane potential (64+/-5.5%; mean+/-SD, n=3), increased levels of cytosolic cytochrome c (8.8+/-0.84 ng/ml; mean+/-SD, n=3), activation of caspase-3 (ca. 3.6-fold) and caspase-9 (ca.1.8-fold), and increased DNA fragmentation (ca. 5-fold), all indicative of apoptosis, were observed in response to exposure to ChSeco. The apoptotic nature of cell death in macrophages was confirmed by dual staining with acridine orange and ethidium bromide. However, unlike the case with cardiomyoblasts and neuronal cells, the apoptotic process in these immune cells was not mediated by increased levels of reactive oxygen species as indicated by a minimal or no increase in 2',7'-dichlorofluorescein fluorescence. It is suggested that the apoptotic process is mediated via the mitochondrial pathway and that ChSeco formed in biological environments contributes to the initiation, progression, and culmination of atherosclerotic plaque formation, as these processes are critically dependent on macrophage apoptosis.

  10. NADPH oxidase derived reactive oxygen species are involved in human neutrophil IL-1β secretion but not in inflammasome activation.

    PubMed

    Gabelloni, María Laura; Sabbione, Florencia; Jancic, Carolina; Fuxman Bass, Juan; Keitelman, Irene; Iula, Leonardo; Oleastro, Matías; Geffner, Jorge R; Trevani, Analía S

    2013-12-01

    Neutrophils are essential players in acute inflammatory responses. Upon stimulation, neutrophils activate NADPH oxidase, generating an array of reactive oxygen species (ROS). Interleukin-1 beta (IL-1β) is a major proinflammatory cytokine synthesized as a precursor that has to be proteolytically processed to become biologically active. The role of ROS in IL-1β processing is still controversial and has not been previously studied in neutrophils. We report here that IL-1β processing in human neutrophils is dependent on caspase-1 and on the serine proteases elastase and/or proteinase 3. NADPH oxidase deficient neutrophils activated caspase-1 and did not exhibit differences in NALP3 expression, indicating that ROS are neither required for inflammasome activation nor for its priming, as has been reported for macrophages. Strikingly, ROS exerted opposite effects on the processing and secretion of IL-1β; whereas ROS negatively controlled caspase-1 activity, as reported in mononuclear phagocytes, ROS were found to be necessary for the exportation of mature IL-1β out of the cell, a role never previously described. The complex ROS-mediated regulation of neutrophil IL-1β secretion might constitute a physiological mechanism to control IL-1β-dependent inflammatory processes where neutrophils play a crucial role.

  11. Involvement of seminal leukocytes, reactive oxygen species, and sperm mitochondrial membrane potential in the DNA damage of the human spermatozoa.

    PubMed

    Lobascio, A M; De Felici, M; Anibaldi, M; Greco, P; Minasi, M G; Greco, E

    2015-03-01

    Measurement of reactive oxygen species (ROS) producing leukocytes in semen has been a standard component of the semen analysis, but its true significance remains still unknown. In this study, we have correlated the number of seminal leukocytes to various semen parameters. We found a negative correlation between the leukocyte number and sperm concentration (rs  = -0.22; p = 0.01) and motility (rs  = -0.20; p = 0.02). In contrast, a positive correlation between the number of leukocytes and both seminal ROS (rs  = 0.70, p < 0.001; n = 125) and the number of spermatozoa with DNA fragmentation (rs  = 0.43, p = 0.032; n = 25) was found. However, only a trend of positive correlation between ROS and the number of spermatozoa with TUNEL-detected DNA fragmentation was observed. Moreover, this latter was not correlated with loss of sperm mitochondrial membrane potential (MMP) (10% vs 35%, rs  = 0.25, p = 0.08; n = 50). Overall these results indicate that the presence of high number of leukocytes in the ejaculate negatively affects key semen parameters, as sperm concentration and motility, associated with infertility conditions. Moreover, they suggest that leukocytes are the major source of the seminal ROS and cause of sperm DNA fragmentation. However, the absence of a clear correlation between ROS and sperm DNA fragmentation, and spermatozoa with damaged DNA and MMP loss, suggest that ROS produced by leukocytes might be not the only cause of DNA damage in spermatozoa and that intrinsic mitochondrial-dependent apoptotic pathways might not have a major impact on sperm DNA fragmentation.

  12. Fires and Burns Involving Home Medical Oxygen

    MedlinePlus

    ... nfpa.org Fires and Burns Involving Home Medical Oxygen The air is normally 21% oxygen. Oxygen is not flammable, but fire needs it to burn. ¾ When more oxygen is present, any fire that starts will burn ...

  13. 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

  14. Involvement of Reactive Oxygen Species in Brominated Diphenyl Ether-47-induced Inflammatory Cytokine Release from Human Extravillous Trophoblasts in vitro

    PubMed Central

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

    2014-01-01

    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 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

  15. Helicobacter pylori Induces Hypermethylation of CpG Islands Through Upregulation of DNA Methyltransferase: Possible Involvement of Reactive Oxygen/Nitrogen Species

    PubMed Central

    Na, Hye-Kyung; Woo, Jeong-Hwa

    2014-01-01

    Helicobacter pylori infection has been considered to be one of the major factors implicated in etiology of gastric cancer. Aberrant DNA methylation accounts for epigenetic modifications induced by H. pylori. H. pylori-induced hypermethylation has been linked to enhancement of the rates of metastasis and recurrence in gastric cancer patients. H. pylori-induced gene hypermethylation has been known to be associated with inflammation. However, the molecular mechanisms underlying H. pylori-induced hypermethylation remain largely unknown. This review highlights possible involvement of reactive oxygen/nitrogen species in H. pylori-induced hypermethylation and gastric carcinogenesis. PMID:25574460

  16. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells.

    PubMed

    Kobashigawa, Shinko; Suzuki, Keiji; Yamashita, Shunichi

    2011-11-04

    Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O(2)(-) production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O(2)(-). Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.

  17. Cytochromes P450 in benzene metabolism and involvement of their metabolites and reactive oxygen species in toxicity

    SciTech Connect

    Gut, I.; Nedelcheva, V.; Soucek, P.

    1996-12-01

    Cytochrome P450 (CYP) 2E1 was the most efficient CYP enzyme that oxidized benzene to soluble and covalently bound metabolites in rat and human liver microsomes. The covalent binding was due mostly to the formation of benzoquinone (BQ), the oxidation product of hydroquinone (HQ), and was inversely related to the formation of soluble metabolites. In rats, inhalation of benzene K mgAiter of air caused a rapid destruction of CYP281 previously induced by phenobarbital. The ability of benzene metabolites to destroy liver microsomal CYP in vitro decreased in the order BQ > HQ > catechol > phenol. The destruction was reversed by ascorbate and diminished by {alpha}-tocopherol, suggesting that HQ was not toxic, whereas BO and serniquinone radical (SO) caused the effect. In the presence of nicotinamide adenine clinucleoticle phosphate, reduced (NADPH) the microsomes did not oxidize HQ to BQ, while the formation of superoxide anion radical from both HQ and BQ was markedly quenched. Destruction of CYP in vitro caused by HQ or BQ was not mediated by hydroxyl radical formation or by lipid peroxiclation. On the contrary, HQ and BQ inhibited NADPH-mediated lipid peroxidation. Ascorbate induced high levels of hydroxyl radical formation and lipid peroxidation, which were differentially affected by quinones, indicating different mechanisms. Despite reducing the toxicity of HQ and BQ, ascorbate appeared to induce its own toxicity, reflected in high levels of lipid peroxiclation. Iron redox cycling played a significant role in the NADPH-induced hydroxyl radical formation but not in that caused by ascorbate; however, lipid peroxiclation induced by NADPH or ascorbate was suppressed by ethylenediaminetraacetate, indicating a crucial role of iron. Thus, the data indicate that the quinones destroyed CYP directly and not via oxygen activation or lipid peroxiclation. 35 refs., 9 figs., 3 tabs.

  18. Additional Evidence of the Trypanocidal Action of (−)-Elatol on Amastigote Forms through the Involvement of Reactive Oxygen Species

    PubMed Central

    Desoti, Vânia Cristina; Lazarin-Bidóia, Danielle; Sudatti, Daniela Bueno; Pereira, Renato Crespo; Ueda-Nakamura, Tania; Nakamura, Celso Vataru; de Oliveira Silva, Sueli

    2014-01-01

    Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action of (−)-elatol, extracted from the macroalga Laurencia dendroidea. However, nothing has been described about the mechanism of action of this compound on amastigotes that are involved in the chronic phase of Chagas’ disease. The goal of the present study was to evaluate the effect of (−)-elatol on the formation of superoxide anions (O2•−), DNA fragmentation, and autophagy in amastigotes of T. cruzi to elucidate the possible mechanism of the trypanocidal action of (−)-elatol. Treatment of the amastigotes with (−)-elatol increased the formation of O2•− at all concentrations of (−)-elatol assayed compared with untreated parasites. Increased fluorescence was observed in parasites treated with (−)-elatol, indicating DNA fragmentation and the formation of autophagic compartments. The results suggest that the trypanocidal action of (−)-elatol might involve the induction of the autophagic and apoptotic death pathways triggered by an imbalance of the parasite’s redox metabolism. PMID:25257785

  19. Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy.

    PubMed

    McMonnies, Charles

    2017-07-28

    This review examines the role of oxidative stress in damage to cells of the trabecular meshwork and associated impaired aqueous drainage as well as damage to retinal ganglion cells and associated visual field losses. Consideration is given to the interaction between vascular and mechanical explanations for pathological changes in glaucoma. For example, elevated intraocular pressure (IOP) forces may contribute to ischaemia but there is increasing evidence that altered blood flow in a wider sense is also involved. Both vascular and mechanical theories are involved through fluctuations in intraocular pressure and dysregulation of blood flow. Retinal function is very sensitive to changes in haemoglobin oxygen concentration and the associated variations in the production of reactive oxygen species. Reperfusion injury and production of reactive oxygen species occurs when IOP is elevated or blood pressure is low and beyond the capacity for blood flow autoregulation to maintain appropriate oxygen concentration. Activities such as those associated with postural changes, muscular effort, eye wiping and rubbing which cause IOP fluctuation, may have significant vascular, mechanical, reperfusion and oxidative stress consequences. Hyperbaric oxygen therapy exposes the eye to increased oxygen concentration and the risk of oxidative damage in susceptible individuals. However, oxygen concentration in aqueous humour, and the risk of damage to trabecular meshwork cells may be greater if hyperbaric oxygen is delivered by a hood which exposes the anterior ocular surface to higher than normal oxygen levels. Oronasal mask delivery of hyperbaric oxygen therapy appears to be indicated in these cases. Copyright © 2017 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  20. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action.

    PubMed

    Fonseca-Silva, Fernanda; Inacio, Job D F; Canto-Cavalheiro, Marilene M; Menna-Barreto, Rubem F S; Almeida-Amaral, Elmo E

    2016-02-01

    The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports further studies of

  1. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action

    PubMed Central

    Fonseca-Silva, Fernanda; Inacio, Job D. F.; Canto-Cavalheiro, Marilene M.; Menna-Barreto, Rubem F. S.; Almeida-Amaral, Elmo E.

    2016-01-01

    Background The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. Methodology/Principal Finding Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health

  2. Endogenous abscisic acid is involved in methyl jasmonate-induced reactive oxygen species and nitric oxide production but not in cytosolic alkalization in Arabidopsis guard cells.

    PubMed

    Ye, Wenxiu; Hossain, Mohammad Anowar; Munemasa, Shintaro; Nakamura, Yoshimasa; Mori, Izumi C; Murata, Yoshiyuki

    2013-09-01

    We recently demonstrated that endogenous abscisic acid (ABA) is involved in methyl jasmonate (MeJA)-induced stomatal closure in Arabidopsis thaliana. In this study, we investigated whether endogenous ABA is involved in MeJA-induced reactive oxygen species (ROS) and nitric oxide (NO) production and cytosolic alkalization in guard cells using an ABA-deficient Arabidopsis mutant, aba2-2, and an inhibitor of ABA biosynthesis, fluridon (FLU). The aba2-2 mutation impaired MeJA-induced ROS and NO production. FLU inhibited MeJA-induced ROS production in wild-type guard cells. Pretreatment with 0.1 μM ABA, which does not induce stomatal closure in the wild type, complemented the insensitivity to MeJA of the aba2-2 mutant. However, MeJA induced cytosolic alkalization in both wild-type and aba2-2 guard cells. These results suggest that endogenous ABA is involved in MeJA-induced ROS and NO production but not in MeJA-induced cytosolic alkalization in Arabidopsis guard cells.

  3. Ionizing radiation accelerates Drp1-dependent mitochondrial fission, which involves delayed mitochondrial reactive oxygen species production in normal human fibroblast-like cells

    SciTech Connect

    Kobashigawa, Shinko; Suzuki, Keiji; Yamashita, Shunichi

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer We report first time that ionizing radiation induces mitochondrial dynamic changes. Black-Right-Pointing-Pointer Radiation-induced mitochondrial fission was caused by Drp1 localization. Black-Right-Pointing-Pointer We found that radiation causes delayed ROS from mitochondria. Black-Right-Pointing-Pointer Down regulation of Drp1 rescued mitochondrial dysfunction after radiation exposure. -- Abstract: Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial O{sub 2}{sup {center_dot}-} production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial O{sub 2}{sup {center_dot}-}. Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation.

  4. Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells.

    PubMed

    Yuan, Guang-Jin; Deng, Jun-Jian; Cao, De-Dong; Shi, Lei; Chen, Xin; Lei, Jin-Ju; Xu, Xi-Ming

    2017-08-14

    To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism. Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species (ROS) were quantified using the fluorescent probe DCFH-DA. Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation. Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

  5. III-10, a newly synthesized flavonoid, induces cell apoptosis with the involvement of reactive oxygen species-mitochondria pathway in human hepatocellular carcinoma cells.

    PubMed

    Dai, Qinsheng; Yin, Qian; Zhao, Yikai; Guo, Ruichen; Li, Zhiyu; Ma, Shiping; Lu, Na

    2015-10-05

    Study of the mechanisms of apoptosis in tumor cells is an important field of tumor therapy and cancer molecular biology. We recently established that III-10, a new flavonoid with a pyrrolidinyl and a benzyl group substitution, exerted its anti-tumor effect via inducing differentiation of human U937 leukemia cells. In this study, we demonstrated that III-10 induced cell apoptosis in human hepatocellular carcinoma cells. The activation of caspase-3, caspase-9, and the increased expression ratio of Bax/Bcl-2 were detected in III-10-induced apoptosis. Z-VAD-FMK, a pan-caspase inhibitor, partly attenuated the apoptotic induction of III-10 on both HepG2 and BEL-7402 cells. Furthermore, the increase of intracellular reactive oxygen species levels and the reduction of mitochondria ΔΨm were also observed in BEL-7402 and HepG2 cells after the treatment of III-10. Pretreatment with NAC, a reactive oxygen species production inhibitor, partly attenuated the apoptosis induced by III-10 via blocking the reactive oxygen species generation. Our data also showed that III-10 induced the release of cytochrome c and AIF to cytosol followed after the reactive oxygen species accumulation. Moreover, the GSH levels and ATP generation were both inhibited after III-10 treatment. Besides, the MAPK, the downstream effect of reactive oxygen species accumulation including JNK could be activated by III-10, as well as the inactivation of ERK. Collectively, the generation of reactive oxygen species might play an crucial role in III-10-induced mitochondrial apoptosis pathway, provided more stubborn evidence for III-10 as a potent anticancer therapeutic candidate. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Curcumin Induces Downregulation of E2F4 Expression and Apoptotic Cell Death in HCT116 Human Colon Cancer Cells; Involvement of Reactive Oxygen Species.

    PubMed

    Kim, Kyung-Chan; Lee, Chuhee

    2010-12-01

    E2F transcription factors and their target genes have been known to play an important role in cell growth control. We found that curcumin, a polyphenolic phytochemical isolated from the plant Curcuma longa, markedly suppressed E2F4 expression in HCT116 colon cancer cells. Hydrogen peroxide was also found to decrease E2F4 protein level, indicating the involvement of reactive oxygen species (ROS) in curucmin-induced downregulation of E2F4 expression. Involvement of ROS in E2F4 downregulation in response to curcumin was confirmed by the result that pretreatment of cells with N-acetylcystein (NAC) before exposure of curcumin almost completely blocked the reduction of E2F4 expression at the protein as well as mRNA level. Anti-proliferative effect of curcumin was also suppressed by NAC which is consistent to previous reports showing curcumin-superoxide production and induction of poly (ADP-ribose) polymerase (PARP) cleavage as well as apoptosis. Expression of several genes, cyclin A, p21, and p27, which has been shown to be regulated in E2F4-dependent manner and involved in the cell cycle progression was also affected by curcumin. Moreover, decreased (cyclin A) and increased (p21 and p27) expression of these E2F4 downstream genes by curcumin was restored by pretreatment of cells with NAC and E2F4 overexpression which is induced by doxycycline. In addition, E2F4 overexpression was observed to partially ameliorate curcumin-induced growth inhibition by cell viability assay. Taken together, we found curcumin-induced ROS down-regulation of E2F4 expression and modulation of E2F4 target genes which finally lead to the apoptotic cell death in HCT116 colon cancer cells, suggesting that E2F4 appears to be a novel determinant of curcumin-induced cytotoxicity.

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

    PubMed Central

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

    2014-01-01

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

  8. Cadmium-induced hydrogen sulfide synthesis is involved in cadmium tolerance in Medicago sativa by reestablishment of reduced (homo)glutathione and reactive oxygen species homeostases.

    PubMed

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

    2014-01-01

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

  9. Toxaphene, but not beryllium, induces human neutrophil chemotaxis and apoptosis via reactive oxygen species (ROS): involvement of caspases and ROS in the degradation of cytoskeletal proteins.

    PubMed

    Lavastre, Valérie; Roberge, Charles J; Pelletier, Martin; Gauthier, Marc; Girard, Denis

    2002-07-01

    Chemicals of environmental concern are known to alter the immune system. Recent data indicate that some contaminants possess proinflammatory properties by activating neutrophils, an area of research that is still poorly investigated. We have previously documented that toxaphene activates human neutrophils to produce reactive oxygen species (ROS) and accelerates apoptosis by a yet unknown mechanism. In this study, we found that toxaphene induces another neutrophil function, chemotaxis. Furthermore, we found that toxaphene induces both chemotaxis and apoptosis via a ROS-dependent mechanism, since these responses were blocked by the addition of catalase to the culture. In addition, toxaphene was found to induce the degradation of the cytoskeletal proteins gelsolin, paxillin, and vimentin during apoptosis, and this was reversed by the addition of z-VAD-FMK (caspase inhibitor) or catalase, demonstrating the importance of caspases and ROS in this process. In contrast to toxaphene, we found that beryllium does not induce superoxide production, and, this correlates with its inability to induce chemotaxis and apoptosis. We conclude that toxaphene induces chemotaxis and apoptosis via ROS and that caspases and ROS are involved in the degradation of cytoskeletal proteins.

  10. The mechanisms involved in seed dormancy alleviation by hydrogen cyanide unravel the role of reactive oxygen species as key factors of cellular signaling during germination.

    PubMed

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

    2009-05-01

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

  11. Integrated signaling network involving calcium, nitric oxide, and active oxygen species but not mitogen-activated protein kinases in BcPG1-elicited grapevine defenses.

    PubMed

    Vandelle, Elodie; Poinssot, Benoît; Wendehenne, David; Bentéjac, Marc; Alain, Pugin

    2006-04-01

    We have already reported the identification of the endopolygalacturonase 1 (BcPG1) from Botrytis cinerea as a potent elicitor of defense responses in grapevine, independently of its enzymatic activity. The aim of the present study is the analysis of the signaling pathways triggered by BcPG1 in grapevine cells. Our data indicate that BcPG1 induces a Ca2+ entry from the apoplasm, which triggers a phosphorylation-dependent nitric oxide (NO) production via an enzyme probably related to a NO synthase. Then NO is involved in (i) cytosolic calcium homeostasis, by activating Ca2+ release from internal stores and regulating Ca2+ fluxes across the plasma membrane, (ii) plasma membrane potential variation, (iii) the activation of active oxygen species (AOS) production, and (iv) defense gene expression, including phenylalanine ammonia lyase and stilbene synthase, which encode enzymes responsible for phytoalexin biosynthesis. Interestingly enough, mitogen-activated protein kinase (MAPK) activation is independent of this regulation pathway that closely connects Ca2+, NO, and AOS.

  12. Grape seed extract triggers apoptosis in Caco-2 human colon cancer cells through reactive oxygen species and calcium increase: extracellular signal-regulated kinase involvement.

    PubMed

    Dinicola, Simona; Mariggiò, Maria Addolorata; Morabito, Caterina; Guarnieri, Simone; Cucina, Alessandra; Pasqualato, Alessia; D'Anselmi, Fabrizio; Proietti, Sara; Coluccia, Pierpaolo; Bizzarri, Mariano

    2013-09-14

    Grape seed extract (GSE) from Italia, Palieri and Red Globe cultivars inhibits cell growth and induces apoptosis in Caco-2 human colon cancer cells in a dose-dependent manner. In order to investigate the mechanism(s) supporting the apoptotic process, we analysed reactive oxygen species (ROS) production, intracellular Ca2+ handling and extracellular signal-regulated kinase (ERK) activation. Upon exposure to GSE, ROS and intracellular Ca2+ levels increased in Caco-2 cells, concomitantly with ERK inactivation. As ERK activity is thought to be essential for promoting survival pathways, inhibition of this kinase is likely to play a relevant role in GSE-mediated anticancer effects. Indeed, pretreatment with N-acetyl cysteine, a ROS scavenger, reversed GSE-induced apoptosis, and promoted ERK phosphorylation. This effect was strengthened by ethylene glycol tetraacetic acid-mediated inhibition of extracellular Ca2+ influx. ROS and Ca2+ influx inhibition, in turn, increased ERK phosphorylation, and hence almost entirely suppressed GSE-mediated apoptosis. These data suggested that GSE triggers a previously unrecognised ERK-based mechanism, involving both ROS production and intracellular Ca2+ increase, eventually leading to apoptosis in cancer cells.

  13. 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

  14. Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux

    PubMed Central

    Tardif, Mélanie R.; Chapeton-Montes, Julie Andrea; Posvandzic, Alma; Pagé, Nathalie; Gilbert, Caroline; Tessier, Philippe A.

    2015-01-01

    S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2 induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K+ exchanges through the ATP-sensitive K+ channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways. PMID:27057553

  15. Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

    SciTech Connect

    Ding, Song-Ze; Yang, Yu-Xiu; Li, Xiu-Ling; Michelli-Rivera, Audrey; Han, Shuang-Yin; Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J.

    2013-05-15

    Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: • We study if Cr(VI) might induce EMT and invasion in epithelial cells. • Cr(VI) induces EMT by altering E-cadherin and vimentin expression. • It also increases cell invasion and promotes oncogenic transformation. • Catalase reduces Cr(VI)-induced EMT, invasion and

  16. Chloroplast-generated reactive oxygen species are involved in hypersensitive response-like cell death mediated by a mitogen-activated protein kinase cascade.

    PubMed

    Liu, Yidong; Ren, Dongtao; Pike, Sharon; Pallardy, Stephen; Gassmann, Walter; Zhang, Shuqun

    2007-09-01

    Plant defense against pathogens often includes rapid programmed cell death known as the hypersensitive response (HR). Recent genetic studies have demonstrated the involvement of a specific mitogen-activated protein kinase (MAPK) cascade consisting of three tobacco MAPKs, SIPK, Ntf4 and WIPK, and their common upstream MAPK kinase (MAPKK or MEK), NtMEK2. Potential upstream MAPKK kinases (MAPKKKs or MEKKs) in this cascade include the orthologs of Arabidopsis MEKK1 and tomato MAPKKKalpha. Activation of the SIPK/Ntf4/WIPK pathway induces cell death with phenotypes identical to pathogen-induced HR at macroscopic, microscopic and physiological levels, including loss of membrane potential, electrolyte leakage and rapid dehydration. Loss of membrane potential in NtMEK2(DD) plants is associated with the generation of reactive oxygen species (ROS), which is preceded by disruption of metabolic activities in chloroplasts and mitochondria. We observed rapid shutdown of carbon fixation in chloroplasts after SIPK/Ntf4/WIPK activation, which can lead to the generation of ROS in chloroplasts under illumination. Consistent with a role of chloroplast-generated ROS in MAPK-mediated cell death, plants kept in the dark do not accumulate H(2)O(2) in chloroplasts after MAPK activation, and cell death is significantly delayed. Similar light dependency was observed in HR cell death induced by tobacco mosaic virus, which is known to activate the same MAPK pathway in an N-gene-dependent manner. These results suggest that activation of the SIPK/Ntf4/WIPK cascade by pathogens actively promotes the generation of ROS in chloroplasts, which plays an important role in the signaling for and/or execution of HR cell death in plants.

  17. Atorvastatin attenuates homocysteine-induced migration of smooth muscle cells through mevalonate pathway involving reactive oxygen species and p38 MAPK.

    PubMed

    Bao, Xiao-mei; Zheng, Hongchao

    2015-08-01

    Statins have been reported to have an antioxidant effect against homocysteine (Hcy)-induced endothelial dysfunction. It is unknown whether they have the same effect against migration of vascular smooth muscle cells (VSMCs) induced by Hcy. In this study, it was investigated whether and how atorvastatin could inhibit the Hcy-induced migration in cultured VSMCs and revealed the possible redox mechanism. VSMCs were isolated from the thoracic aortas of Sprague-Dawley rats. The migration of VSMCs was examined using a transwell technique and cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay. Reactive oxygen species (ROS) were measured using the fluoroprobe 2'7'-dichlorodihydrofluorescein diacetate. The activity of NADPH oxidase was assessed by lucigenin enhanced chemiluminescence. Expressions of Nox1 mRNA and p-p38MAPK protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. The results showed that atorvastatin inhibited the migration of VSMCs induced by Hcy, which was reversed by the mevalonate. In addition, pretreatment with the NADPH oxidase inhibitor DPI, the free radical scavenger NAC and the p38 MAPK inhibitor SB203580 blocked Hcy-induced VSMCs migration. Furthermore, atorvastatin suppressed Hcy-induced activation of NADPH oxidase and ROS, attenuated Hcy-induced overexpression of Nox1mRNA. Similar effects occurred with VSMCs transfected with Nox1 siRNA. Moreover, atorvastatin other than DPI, NAC, SB203580 and Nox1 siRNA transfection blocked Hcy-induced p38 MAPK phosphorylation, which was also reversed by the mevalonate. The data demonstrates that atorvastatin inhibits Hcy-induced VSMCs migration in a mevalonate pathway. Furthermore, a part of the biological effect of atorvastatin involves a decrease in the levels of Nox1-dependent ROS generation and p38 MAPK activation.

  18. Cucurbitacin L 2-O-β-Glucoside Demonstrates Apoptogenesis in Colon Adenocarcinoma Cells (HT-29): Involvement of Reactive Oxygen and Nitrogen Species Regulation

    PubMed Central

    Abdelwahab, Siddig Ibrahim; Hassan, Loiy Elsir Ahmed; Abdul Majid, Amin M. S.; Yagi, Sakina M. Ahmed; Mohan, Syam; Elhassan Taha, Manal Mohamed; Ahmad, Syahida; Chuen, Cheah Shiau; Narrima, Putri; Rais, Mohd Mustafa; Syam, Suvitha; Moharam, Bushra Abdulkarim; Hadi, A. Hamid A.

    2012-01-01

    Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results revealed that CLG was cytotoxic to HT-29. CLG increased significantly (P < 0.05) RNA and protein levels of caspase-3 in HT-29 cells when verified using a colorimetric assay and realtime qPCR, respectively. The results showed that lipopolysaccharide/interferon-gamma (LPS/INF-γ) increased nitrous oxide (NO) production inR AW264.7macrophages, whereas N(G)-nitro-L-argininemethyl ester (L-NAME) and CLG curtailed it. This compound did not reveal any cytotoxicity on RAW264.7 macrophages and human normal liver cells (WRL-68) when tested using the MTT assay. Findings of ferric reducing antioxidant power (FRAP) and oxygen radical absorption capacity (ORAC) assays demonstrate the antioxidant properties of CLG. The apoptogenic property of CLG on HT-29 cells is thus related to inhibition of reactive nitrogen and oxygen reactive species and the triggering of caspase-3-regulated apoptosis. PMID:22685485

  19. 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

  20. REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE

    PubMed Central

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

    2014-01-01

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

  1. A newly discovered oxidant defence system and its involvement in the development of Aurelia aurita (Scyphozoa, Cnidaria): reactive oxygen species and elemental iodine control medusa formation.

    PubMed

    Berking, Stefan; Czech, Nicole; Gerharz, Melanie; Herrmann, Klaus; Hoffmann, Uwe; Raifer, Hartmann; Sekul, Guy; Siefker, Barbara; Sommerei, Andrea; Vedder, Fritz

    2005-01-01

    In Aurelia aurita, applied iodine induces medusa formation (strobilation). This process also occurs when the temperature is lowered. This was found to increase oxidative stress resulting in an increased production of iodine from iodide. One polyp produces several medusae (initially termed ephyrae) starting at the polyp's oral end. The spreading of strobilation down the body column is controlled by a feedback loop: ephyra anlagen decrease the tyrosine content in adjacent polyp tissue by producing melanin from tyrosine. Endogenous tyrosine is able to remove iodine by forming iodiferous tyrosine compounds. The reduced level of tyrosine causes the ephyra-polyp-border to move towards the basal end of the former polyp. We argue that an oxidant defence system may exist which makes use of iodide and tyrosine. Like other marine invertebrates, polyps of Aurelia contain iodide ions. Inevitably produced peroxides oxidise iodide into iodine. The danger to be harmed by iodine is strongly decreased by endogenous tyrosine which reacts with iodine to form iodiferous tyrosine compounds including thyroxin. Both substances together, iodide and tyrosine, form an efficient oxidant defence system which shields the tissue against damage by reactive oxygen species. In the course of evolution (from a species at the basis of the animal kingdom like Aurelia to a highly evolved species like man) the waste product thyroxin (indicating a high metabolic rate) has developed into a hormone which controls the metabolic rate.

  2. Formation of long-lived reactive species of blood serum proteins induced by low-intensity irradiation of helium-neon laser and their involvement in the generation of reactive oxygen species.

    PubMed

    Ivanov, Vladimir E; Usacheva, Anna M; Chernikov, Anatoly V; Bruskov, Vadim I; Gudkov, Sergey V

    2017-09-14

    It was demonstrated that low-intensity radiation of helium-neon (He-Ne) laser at 632.8nm, which leads to the transition of oxygen to a singlet state, causes the formation of reactive oxygen species (ROS) - hydrogen peroxide, hydroxyl and superoxide (hydroperoxide) radicals - in aqueous solutions. The oxygen effect - dependence of hydrogen peroxide formation on the concentration of molecular oxygen - was shown, and the participation of singlet oxygen, hydroxyl radicals and superoxide (hydroperoxide) radicals in this process was testified. Laser radiation-induced ROS in solutions of blood serum proteins, bovine serum albumin and bovine gamma-globulin, cause the formation of long-lived reactive protein species (LRPS) with a half-life of about 4h. The generation of LRPS caused by laser irradiation results in prolonged several-hour generation of ROS - hydrogen peroxide, hydroxyl and superoxide radicals. As affected by LRPS, coupled radical reactions lead to conversion of dissolved molecular oxygen to hydrogen peroxide. Irradiation with light sources away from the oxygen absorption band is not attended by formation of ROS and LRPS. A consideration is provided for the possible molecular mechanisms of ROS formation under the influence of He-Ne laser irradiation, the role of proteins in their generation and the biological significance of these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Reactive oxygen species in the immune system.

    PubMed

    Yang, Yuhui; Bazhin, Alexandr V; Werner, Jens; Karakhanova, Svetlana

    2013-06-01

    Reactive oxygen species (ROS) are a group of highly reactive chemicals containing oxygen produced either exogenously or endogenously. ROS are related to a wide variety of human disorders, such as chronic inflammation, age-related diseases and cancers. Besides, ROS are also essential for various biological functions, including cell survival, cell growth, proliferation and differentiation, and immune response. At present there are a number of excellent publications including some reviews about functions of these molecules either in normal cell biology or in pathophysiology. In this work, we reviewed available information and recent advances about ROS in the main immune cell types and gave summary about functions of these highly reactive molecules both in innate immunity as conservative defense mechanisms and in essential immune cells involved in adaptive immunity, and particularly in immune suppression.

  4. Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: Involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways.

    PubMed

    He, Hong; Wang, Songhai; Tian, Jiyu; Chen, Lei; Zhang, Wei; Zhao, Junjie; Tang, Haifeng; Zhang, Xiaojun; Chen, Jianzong

    2015-11-15

    Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress-induced neuron loss is thought to play a crucial role in the pathogenesis of PD. Previous work from our group suggests that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from a traditional Chinese herb, Polygonum multiflorum thunb, can attenuate 1-methyl-4-phenyl pyridium-induced apoptosis in the neuronal cell line PC12, by inhibiting reactive oxygen species generation and modulating c-Jun N-terminal kinases (JNK) activation. Here, we investigated the protective effects of TSG against 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced loss of tyrosine hydroxylase positive cells in mice and the underlying mechanisms. The results showed that MPTP-induced loss of tyrosine hydroxylase positive cells and reactive oxygen species generation were prevented by TSG in a dose-dependent manner. The reactive oxygen species scavenger N-acetylcysteine could also mitigate reactive oxygen species generation. Moreover, JNK and P38 were activated by MPTP, but extracellular signal-regulated protein kinases phosphorylation did not change after MPTP treatment. TSG at different doses blocked the activation of JNK and P38. The protective effect of TSG was also associated with downregulation of the bax/bcl-2 ratio, reversed the release of cytochrome c and smac, and inhibited the activation of caspase-3, -6, and -9 induced by MPTP. In conclusion, our studies demonstrated that the protective effects of TSG in the MPTP-induced mouse model of PD are involved, at least in part, in controlling reactive oxygen species-mediated JNK, P38, and mitochondrial pathways.

  5. The nitric oxide prodrug JS-K is effective against non-small-cell lung cancer cells in vitro and in vivo: involvement of reactive oxygen species.

    PubMed

    Maciag, Anna E; Chakrapani, Harinath; Saavedra, Joseph E; Morris, Nicole L; Holland, Ryan J; Kosak, Ken M; Shami, Paul J; Anderson, Lucy M; Keefer, Larry K

    2011-02-01

    Non-small-cell lung cancer is among the most common and deadly forms of human malignancies. Early detection is unusual, and there are no curative therapies in most cases. Diazeniumdiolate-based nitric oxide (NO)-releasing prodrugs are a growing class of promising NO-based therapeutics. Here, we show that O(2)-(2,4-dinitrophenyl)-1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) is a potent cytotoxic agent against a subset of human non-small-cell lung cancer cell lines both in vitro and as xenografts in mice. JS-K treatment led to 75% reduction in the growth of H1703 lung adenocarcinoma cells in vivo. Differences in sensitivity to JS-K in different lung cancer cell lines seem to be related to their endogenous levels of reactive oxygen species (ROS)/reactive nitrogen species (RNS). Other related factors, levels of peroxiredoxin 1 (PRX1) and 8-oxo-deoxyguanosine glycosylase (OGG1), also correlated with drug sensitivity. Treatment of the lung adenocarcinoma cells with JS-K resulted in oxidative/nitrosative stress in cells with high basal levels of ROS/RNS, which, combined with the arylating properties of the compound, was reflected in glutathione depletion and alteration in cellular redox potential, mitochondrial membrane permeabilization, and cytochrome c release. Inactivation of manganese superoxide dismutase by nitration was associated with increased superoxide and significant DNA damage. Apoptosis followed these events. Taken together, the data suggest that diazeniumdiolate-based NO-releasing prodrugs may have application as a personalized therapy for lung cancers characterized by high levels of ROS/RNS. PRX1 and OGG1 proteins, which can be easily measured, could function as biomarkers for identifying tumors sensitive to the therapy.

  6. Reactive oxygen species production by human dendritic cells involves TLR2 and dectin-1 and is essential for efficient immune response against Mycobacteria.

    PubMed

    Romero, María Mercedes; Basile, Juan Ignacio; Corra Feo, Laura; López, Beatriz; Ritacco, Viviana; Alemán, Mercedes

    2016-06-01

    Tuberculosis remains the single largest infectious disease with 10 million new cases and two million deaths that are estimated to occur yearly, more than any time in history. The intracellular replication of Mycobacterium tuberculosis (Mtb) and its spread from the lungs to other sites occur before the development of adaptive immune responses. Dendritic cells (DC) are professional antigen-presenting cells whose maturation is critical for the onset of the protective immune response against tuberculosis disease and may vary depending on the nature of the cell wall of Mtb strain. Here, we describe the role of the endogenous production of reactive oxygen species (ROS) on DC maturation and expansion of Mtb-specific lymphocytes. Here, we show that Mtb induces DC maturation through TLR2/dectin-1 by generating of ROS and through Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) in a ROS independently manner. Based on the differences observed in the ability to induce DC maturation, ROS production and lymphocyte proliferation by those Mtb families widespread in South America, i.e., Haarlem and Latin American Mediterranean and the reference strain H37Rv, we propose that variance in ROS production might contribute to immune evasion affecting DC maturation and antigen presentation.

  7. Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species

    PubMed Central

    Julio-Amilpas, Alberto; Montiel, Teresa; Soto-Tinoco, Eva; Gerónimo-Olvera, Cristian; Massieu, Lourdes

    2015-01-01

    Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury. PMID:25649993

  8. 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

  9. The pepper calmodulin gene CaCaM1 is involved in reactive oxygen species and nitric oxide generation required for cell death and the defense response.

    PubMed

    Choi, Hyong Woo; Lee, Dong Hyuk; Hwang, Byung Kook

    2009-11-01

    Calcium signaling has emerged as an important signal transduction pathway of higher plants in response to biotic and abiotic stresses. Ca2+-bound calmodulin (CaM) plays a critical role in decoding and transducing stress signals by activating specific targets. Here, we isolated and functionally characterized the pathogen-responsive CaM gene, Capsicum annuum calmodulin 1 (CaCaM1), from pepper (C. annuum) plants. The cellular function of CaCaM1 was verified by Agrobacterium spp.-mediated transient expression in pepper and transgenic overexpression in Arabidopsis thaliana. Agrobacterium spp.-mediated transient expression of CaCaM1 activated reactive oxygen species (ROS), nitric oxide (NO) generation, and hypersensitive response (HR)-like cell death in pepper leaves, ultimately leading to local acquired resistance to Xanthomonas campestris pv. vesicatoria. CaCaM1-overexpression (OX) Arabidopsis exhibited enhanced resistance to Pseudomonas syringae and Hyaloperonospora parasitica, which was accompanied by enhanced ROS and NO generation and HR-like cell death. Treatment with the calcium-channel blocker suppressed the oxidative and NO bursts and HR-like cell death that were triggered by CaCaM1 expression in pepper and Arabidopsis, suggesting that calcium influx is required for the activation of CaCaM1-mediated defense responses in plants. Upon treatment with the CaM antagonist, virulent P. syringae pv. tomato-induced NO generation was also compromised in CaCaM1-OX leaves. Together, these results suggest that the CaCaM1 gene functions in ROS and NO generation are essential for cell death and defense responses in plants.

  10. Differential involvement of various sources of reactive oxygen species in thyroxin-induced hemodynamic changes and contractile dysfunction of the heart and diaphragm muscles

    PubMed Central

    Elnakish, Mohammad T.; Schultz, Eric J.; Gearinger, Rachel L.; Saad, Nancy S.; Rastogi, Neha; Ahmed, Amany A.E.; Mohler, Peter J.; Janssen, Paul M.L.

    2015-01-01

    Thyroid hormones are key regulators of basal metabolic state and oxidative metabolism. Hyperthyroidism has been reported to cause significant alterations in hemodynamics, and in cardiac and diaphragm muscle function, all of which have been linked to increased oxidative stress. However, the definite source of increased reactive oxygen species (ROS) in each of these phenotypes is still unknown. The goal of the current study was to test the hypothesis that thyroxin (T4) may produce distinct hemodynamic, cardiac, and diaphragm muscle abnormalities by differentially affecting various sources of ROS. Wild-type and T4 mice with and without 2-week treatments with allopurinol (xanthine oxidase inhibitor), apocynin (NADPH oxidase inhibitor), L-NIO (nitric oxide synthase inhibitor), or MitoTEMPO (mitochondria-targeted antioxidant) were studied. Blood pressure and echocardiography were noninvasively evaluated, followed by ex vivo assessments of isolated heart and diaphragm muscle functions. Treatment with L-NIO attenuated the T4-induced hypertension in mice. However, apocynin improved the left-ventricular (LV) dysfunction without preventing the cardiac hypertrophy in these mice. Both allopurinol and MitoTEMPO reduced the T4-induced fatigability of the diaphragm muscles. In conclusion, we show here for the first time that T4 exerts differential effects on various sources of ROS to induce distinct cardiovascular and skeletal muscle phenotypes. Additionally, we find that T4-induced LV dysfunction is independent of cardiac hypertrophy and NADPH oxidase is a key player in this process. Furthermore, we prove the significance of both xanthine oxidase and mitochondrial ROS pathways in T4-induced fatigability of diaphragm muscles. Finally, we confirm the importance of the nitric oxide pathway in T4-induced hypertension. PMID:25795514

  11. Involvement of reactive oxygen species and high-voltage-activated calcium currents in nanoparticle zinc oxide-induced cytotoxicity in vitro

    NASA Astrophysics Data System (ADS)

    Zhao, Jingxia; Yao, Yang; Liu, Shichang; Zhang, Tao; Ren, Guogang; Yang, Zhuo

    2012-11-01

    This study was to determine the possible neurotoxicity and mechanisms underlying the effects of nano-ZnO with sizes of 20-80 nm on central nervous system (CNS). The cytotoxicity of nano-ZnO was investigated in PC12 cells. The viability of cells was observed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the generation of reactive oxygen species (ROS) for cells was evaluated by a fluorometry assay. The apoptosis of cells was detected and analyzed by flow cytometry. In addition, effects of nano-ZnO on the properties of high-voltage-activated (HVA) calcium currents were studied in acutely isolated rat hippocampal pyramidal neurons using the whole-cell patch clamp technique. The results of MTT assay showed that nano-ZnO (10-4 g/mL) caused a significant decrease in cell viability ( P < 0.05). Nano-ZnO induced intracellular accumulation of ROS and the apoptosis of PC12 cells with the increasing concentration of nano-ZnO in flow cytometric assay ( P < 0.05). Further results of electrophysiological recording indicated that 10-4 g/mL nano-ZnO first altered the current-voltage curve and the peak amplitudes of HVA calcium currents at 10 min of the recording, and the peak current amplitudes were increased significantly at the end of 30 min ( P < 0.05). All these results suggested that the increase of intracellular ROS was one of potential mechanisms of cellular apoptosis induced by nano-ZnO. Nano-ZnO could cause the elevation of cytosolic calcium levels by enhancement of HVA calcium currents, which would increase the generation of intracellular ROS, and consequently promote the neuronal apoptosis.

  12. Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles

    PubMed Central

    Valavanidis, Athanasios; Vlachogianni, Thomais; Fiotakis, Konstantinos

    2009-01-01

    Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS) in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR) and spin-trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2•−) and hydroxyl (HO•) radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT) solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2’-deoxyguanosine (a biomarker for carcinogenesis). Also, we observed synergistic effects in the generation of HO•, through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc.) and ambient particulate matter (PM), such as PM10, PM2.5 and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM2.5 and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and “bio-filters” with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase. PMID:19440393

  13. Complex cellular responses to reactive oxygen species.

    PubMed

    Temple, Mark D; Perrone, Gabriel G; Dawes, Ian W

    2005-06-01

    Genome-wide analyses of yeast provide insight into cellular responses to reactive oxygen species (ROS). Many deletion mutants are sensitive to at least one ROS, but no one oxidant is representative of 'oxidative stress' despite the widespread use of a single compound such as H(2)O(2). This has major implications for studies of pathological situations. Cells have a range of mechanisms for maintaining resistance that involves either induction or repression of many genes and extensive remodeling of the transcriptome. Cells have constitutive defense systems that are largely unique to each oxidant, but overlapping, inducible repair systems. The pattern of the transcriptional response to a particular ROS depends on its concentration, and 'classical' antioxidant systems that are induced by high concentrations of ROS can be repressed when cells adapt to low concentrations of ROS.

  14. Effects of Benzo(e)pyrene on Reactive Oxygen/Nitrogen Species and Inflammatory Cytokines Induction in Human RPE Cells and Attenuation by Mitochondrial-involved Mechanism

    PubMed Central

    Estrago-Franco, M. Fernanda; Moustafa, M. Tarek; Riazi-Esfahani, Mohammad; Sapkal, Ashish U.; Piche-Lopez, Rhina; Patil, A. Jayaprakash; Sharma, Ashish; Falatoonzadeh, Payam; Chwa, Marilyn; Luczy-Bachman, Georgia; Kuppermann, Baruch D.; Kenney, M. Cristina

    2016-01-01

    Purpose: To identify inhibitors that could effectively lower reactive oxygen/nitrogen species (ROS/RNS), complement and inflammatory cytokine levels induced by Benzo(e)pyrene [B(e)p], an element of cigarette smoke, in human retinal pigment epithelial cells (ARPE-19) in vitro. Methods: ARPE-19 cells were treated for 24 hours with 200 μM, 100 μM, and 50 μM B(e)p or DMSO (dimethyl sulfoxide)-equivalent concentrations. Some cultures were pre-treated with ROS/RNS inhibitors (NG nitro-L-arginine, inhibits nitric oxide synthase; Apocynin, inhibits NADPH oxidase; Rotenone, inhibits mitochondrial complex I; Antimycin A, inhibits mitochondria complex III) and ROS/RNS levels were measured with a fluorescent H2 DCFDA assay. Multiplex bead arrays were used to measure levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), Transforming Growth Factor alpha (TGF-α) and Vascular Endothelial Growth Factor (VEGF). IL-6 levels were also measured by an enzyme-linked immunosorbent assay. Real-time qPCR analyses were performed with primers for C3 (component 3), CFH (inhibits complement activation), CD59 (inhibitor of the complement membrane attack complex (MAC)) and CD55/DAF (accelerates decay of target complement target proteins). Results: The ARPE-19 cultures treated with B(e)p showed significantly increased ROS/RNS levels (P < 0.001), which were then partially reversed by 6 μM Antimycin A (19%, P = 0.03), but not affected by the other ROS/RNS inhibitors. The B(e)p treated cultures demonstrated increased levels of IL-6 (33%; P = 0.016) and GM-CSF (29%; P = 0.0001) compared to DMSO-equivalent controls, while the expression levels for components of the complement pathway (C3, CFH, CD59 and CD55/DAF) were not changed. Conclusion: The cytotoxic effects of B(e)p include elevated ROS/RNS levels along with pro-inflammatory IL-6 and GM-CSF proteins. Blocking the Qi site of cytochrome c reductase (complex III) with Antimycin A led to

  15. The Effect of (-)-Epigallocatechin 3-O - Gallate In Vitro and In Vivo in Leishmania braziliensis: Involvement of Reactive Oxygen Species as a Mechanism of Action

    PubMed Central

    Inacio, Job D. F.; Gervazoni, Luiza; Canto-Cavalheiro, Marilene M.; Almeida-Amaral, Elmo E.

    2014-01-01

    Background Leishmaniasis is a parasitic disease associated with extensive mortality and morbidity. The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. Natural compounds have been used as novel treatments for parasitic diseases. In this paper, we evaluated the effect of (-)-epigallocatechin 3-O-gallate (EGCG) on Leishmania braziliensis in vitro and in vivo and described the mechanism of EGCG action against L. braziliensis promastigotes and intracellular amastigotes. Methodology/Principal Finding In vitro activity and reactive oxygen species (ROS) measurements were determined during the promastigote and intracellular amastigote life stages. The effect of EGCG on mitochondrial membrane potential (ΔΨm) was assayed using JC-1, and intracellular ATP concentrations were measured using a luciferin-luciferase system. The in vivo experiments were performed in infected BALB/c mice orally treated with EGCG. EGCG reduced promastigote viability and the infection index in a time- and dose-dependent manner, with IC50 values of 278.8 µM and 3.4 µM, respectively, at 72 h and a selectivity index of 149.5. In addition, EGCG induced ROS production in the promastigote and intracellular amastigote, and the effects were reversed by polyethylene glycol (PEG)-catalase. Additionally, EGCG reduced ΔΨm, thereby decreasing intracellular ATP concentrations in promastigotes. Furthermore, EGCG treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study demonstrates the leishmanicidal effects of EGCG against the two forms of L. braziliensis, the promastigote and amastigote. In addition, EGCG promotes ROS production as a part of its mechanism of action, resulting in decreased ΔΨm and reduced intracellular ATP concentrations. These actions ultimately

  16. Phytate, reactive oxygen species and colorectal cancer.

    PubMed

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

    1998-05-01

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

  17. The oxygen isotope equilibrium fractionation between sulfite species and water

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  18. Mitochondrial Reactive Oxygen Species and Photodynamic Therapy

    PubMed Central

    Ito, Hiromu

    2016-01-01

    Worldwide, the number of cancer cases is increasing. Typically, they are treated by either surgery or chemotherapy. However, these treatments may be undesirable in elderly patients or those who are under medication with antiplatelet drugs. Photodynamic therapy (PDT) represents a potentially attractive treatment option for these types of patients, since it does not involve surgery and has considerably reduced side effects compared to chemotherapy. Porphyrin, one of the most commonly used photosensitizers, has the convenient property of cancer-specific accumulation and therefore, is commonly used in PDT. However, the mechanism by which this cancer-specific accumulation occurs remains unclear. We previously reported that a heme-transport protein, HCP1, was capable of transporting porphyrin compounds. HCP1 expression is associated with increased hypoxia, although the detailed mechanism by which this regulation occurs is also unknown. Here, we review available data on the mechanism of regulation of HCP1 expression through mitochondrial reactive oxygen species (mitROS). Specifically, cancer cells show increased expression of HCP1 compared to normal cells and this over-expression is reduced in cancer cells over-expressing the mitROS scavenging enzyme manganese superoxide dismutase (MnSOD). Thus we conclude that mitROS is involved in regulating HCP1 expression. PMID:27853344

  19. Rosacea, reactive oxygen species, and azelaic Acid.

    PubMed

    Jones, David A

    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.

  20. 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

  1. Implication of signaling pathways involving calcium, phosphorylation and active oxygen species in methyl jasmonate-induced defense responses in grapevine cell cultures.

    PubMed

    Faurie, Bertrand; Cluzet, Stéphanie; Mérillon, Jean-Michel

    2009-11-15

    Perception of elicitors triggers plant defense responses via various early signal transduction pathways. Methyl jasmonate (MeJA) stimulates defense responses in grapevine (Vitis vinifera). We investigated the involvement of various partners (calcium, ROS, reversible phosphorylation) in MeJA-induced responses by using a pharmacological approach. We used specific calcium channel effectors and inhibitors of serine/threonine phosphatases, superoxide dismutase and NAD(P)H oxidase and investigated production of stilbenes (resveratrol and its glucoside, piceid, the major form), which are the grapevine phytoalexins. RNA accumulation of two genes encoding enzymes involved in stilbene synthesis (PAL and STS), three genes encoding pathogenesis-related proteins (CHIT4C, PIN and GLU) and one gene encoding an enzyme producing jasmonates (LOX) were also assessed. Calcium and its origin seemed to play a major role in MeJA-induced grapevine defense responses. Phytoalexin production was strongly affected if calcium from the influx plasma membrane was inhibited, whereas calcium from the intracellular compartments did not seem to be involved. ROS production seemed to interfere with MeJA-stimulated defense responses, and protein phosphorylation/dephosphorylation events also played a direct role.

  2. 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.

  3. Spectroscopically Characterized Synthetic Mononuclear Nickel-Oxygen Species.

    PubMed

    Corona, Teresa; Company, Anna

    2016-09-12

    Iron, copper, and manganese are the predominant metals found in oxygenases that perform efficient and selective hydrocarbon oxidations and for this reason, a large number of the corresponding metal-oxygen species has been described. However, in recent years nickel has been found in the active site of enzymes involved in oxidation processes, in which nickel-dioxygen species are proposed to play a key role. Owing to this biological relevance and to the existence of different catalytic protocols that involve the use of nickel catalysts in oxidation reactions, there is a growing interest in the detection and characterization of nickel-oxygen species relevant to these processes. In this Minireview the spectroscopically/structurally characterized synthetic superoxo, peroxo, and oxonickel species that have been reported to date are described. From these studies it becomes clear that nickel is a very promising metal in the field of oxidation chemistry with still unexplored possibilities.

  4. 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…

  5. 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…

  6. Ethylene promotes germination of Arabidopsis seed under salinity by decreasing reactive oxygen species: evidence for the involvement of nitric oxide simulated by sodium nitroprusside.

    PubMed

    Lin, Yingchao; Yang, Lei; Paul, Matthew; Zu, Yuangang; Tang, Zhonghua

    2013-12-01

    Both ethylene and nitric oxide (NO) are involved in modulating seed germination in adverse environments. However, the mechanisms by which they interact and affect germination have not been explained. In this study, the relationship between ethylene and NO during germination of Arabidopsis seed under salinity was analysed. Application of exogenous 1-aminocyclopropane-1-carboxylate (ACC, a precursor of ethylene biosynthesis) or sodium nitroprusside (SNP, an NO donor) largely overcame the inhibition of germination induced by salinity. The effects of ACC and SNP were decreased by 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO), a specific NO scavenger, or by aminoisobutyric acid (AIB), an inhibitor of ethylene biosynthesis, indicating that ethylene and NO interact during germination under salinity. Further, we demonstrated that ACC increased NO production and that SNP greatly induced the expression of the ACS2 gene involved in ethylene synthesis in Arabidopsis seeds germinating under salinity stress, suggesting that each substance influences the production of the other. Application of exogenous ACC increased germination under oxidative stress induced by hydrogen peroxide (H2O2) while SNP had a much smaller effect on wild-type Arabidopsis (Col-0) and no effect on the ethylene insensitive mutant (ein3-1) seeds, respectively. This shows that NO increased germination under salinity indirectly through H2O2 acting via the ethylene pathway. The endogenous concentration of H2O2 was increased by salinity in germinating seeds but was decreased by exogenous ACC, which stimulated germination ultimately. To explain all these results and the regulation of germination of Arabidopsis seed under salinity we propose a model involving ethylene, NO and H2O2 interaction. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. 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.

  8. Reactive Oxygen Species Regulate Oxygen-Sensitive Potassium Flux in Rainbow Trout Erythrocytes

    PubMed Central

    Bogdanova, Anna Yu; Nikinmaa, Mikko

    2001-01-01

    In the present study, we have investigated if reactive oxygen species are involved in the oxygen-dependent regulation of potassium-chloride cotransport activity in trout erythrocyte membrane. An increase in the oxygen level caused an increase in chloride-sensitive potassium transport (K+-Cl− cotransport). 5 mM hydrogen peroxide caused an increase in K+-Cl− cotransport at 5% oxygen. The increase in flux could be inhibited by adding extracellular catalase in the incubation. Pretreatment of the cells with mercaptopropionyl glycine (MPG), a scavenger of reactive oxygen species showing preference for hydroxyl radicals, abolished the activation of the K+-Cl− cotransporter by increased oxygen levels. The inhibition by MPG was reversible, and MPG could not inhibit the activation of transporter by the sulfhydryl reagent, N-ethylmaleimide, indicating that the effect of MPG was due to the scavenging of reactive oxygen species and not to the reaction of MPG with the cotransporter. Copper ions, which catalyze the production of hydroxyl radicals in the Fenton reaction, activated K+-Cl− cotransport significantly at hypoxic conditions (1% O2). These data suggest that hydroxyl radicals, formed from O2 in close vicinity to the cell membrane, play an important role in the oxygen-dependent activation of the K+-Cl− cotransporter. PMID:11158169

  9. Reactive oxygen species in phagocytic leukocytes

    PubMed Central

    2008-01-01

    Phagocytic leukocytes consume oxygen and generate reactive oxygen species in response to appropriate stimuli. The phagocyte NADPH oxidase, a multiprotein complex, existing in the dissociated state in resting cells becomes assembled into the functional oxidase complex upon stimulation and then generates superoxide anions. Biochemical aspects of the NADPH oxidase are briefly discussed in this review; however, the major focus relates to the contributions of various modes of microscopy to our understanding of the NADPH oxidase and the cell biology of phagocytic leukocytes. PMID:18597105

  10. 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

  11. 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

  12. Antimicrobial Actions of Reactive Oxygen Species

    PubMed Central

    Fang, Ferric C.

    2011-01-01

    ABSTRACT Everything should be as simple as it can be, but not simpler.—Attributed to Albert Einstein (1) Reactive oxygen species (ROS) are produced by host phagocytes and exert antimicrobial actions against a broad range of pathogens. The observable antimicrobial actions of ROS are highly dependent on experimental conditions. This perspective reviews recent controversies regarding ROS in Salmonella-phagocyte interactions and attempts to reconcile conflicting observations from different laboratories. PMID:21896680

  13. A Reaction Involving Oxygen and Metal Sulfides.

    ERIC Educational Resources Information Center

    Hill, William D. Jr.

    1986-01-01

    Describes a procedure for oxygen generation by thermal decomposition of potassium chlorate in presence of manganese dioxide, reacted with various sulfides. Provides a table of sample product yields for various sulfides. (JM)

  14. A Reaction Involving Oxygen and Metal Sulfides.

    ERIC Educational Resources Information Center

    Hill, William D. Jr.

    1986-01-01

    Describes a procedure for oxygen generation by thermal decomposition of potassium chlorate in presence of manganese dioxide, reacted with various sulfides. Provides a table of sample product yields for various sulfides. (JM)

  15. The solid Earth's involvement in oxygen cycling: Observations and theory

    NASA Astrophysics Data System (ADS)

    Shorttle, O.; Stolper, E.; Antoshechkina, P. M.; Asimow, P. D.; Jennings, E. S.; Gaetani, G. A.; Graham, D. W.; Hartley, M. E.; Williams, H. M.; Brounce, M. N.; Halldorsson, S. A.

    2016-12-01

    Interactions between the hydrosphere, atmosphere, and silicate portion of Earth regulate atmospheric oxygen. Whilst oxygen is produced by photosynthesis, its buildup in the atmosphere is regulated by oxidation of organic matter, reduced volcanic gasses, and the ferrous iron in silicates. We focus on this latter part of the abiotic oxygen cycle, and interrogate with new observations and modelling the long term cycling of oxygen between the mantle and atmosphere via ocean crust formation, oxidation, subduction, and its eventual inclusion in the source regions of hotspots. We present new Fe-XANES measurements on basalts from three localities: two mid-ocean ridges (MOR) free from hotspot influence, Juan de Fuca and the South East Indian Ridges; and one plume locality exhibiting significant geochemical heterogeneity, Iceland. These samples constrain the redox heterogeneity of their respective mantle source regions and the processes involved in ferric iron transfer from the mantle into basalts. The MORs erupt basalts with very uniform ferric iron proportions, despite their exhibiting large changes in ridge axial depth and geochemical variability. In contrast, Icelandic basalts vary widely in their ferric iron proportions, and are systematically more oxidised than MOR basalts by 0.8 log units. We find that the Icelandic mantle contains oxidised domains with the major element, trace element, and isotopic signatures of recycled basalt components. These geochemical characteristics support a model in which alteration of oceanic crust provides a long-term sink for oxygen in the deep mantle. Complementary to the observational work, we perform new thermodynamic calculations characterising the behaviour of ferric iron during mantle melting. These models enable us to identify what aspects of basalt ferric iron are attributable to melting processes as opposed to source composition. The models' prediction of basalt ferric iron contents decreasing with increasing mantle potential

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

    PubMed

    Li, Hui; Jubelirer, Sara; Garcia Costas, Amaya M; Frigaard, Niels-Ulrik; Bryant, Donald A

    2009-11-01

    The genome of the green sulfur bacterium Chlorobaculum (Cba.) tepidum, a strictly anaerobic photolithoautotroph, is predicted to encode more than ten genes whose products are potentially involved in protection from reactive oxygen species and an oxidative stress response. The encoded proteins include cytochrome bd quinol oxidase, NADH oxidase, rubredoxin oxygen oxidoreductase, several thiol peroxidases, alkyl hydroperoxide reductase, superoxide dismutase, methionine sulfoxide reductase, and rubrerythrin. To test the physiological functions of some of these proteins, ten genes were insertionally inactivated. Wild-type Cba. tepidum cells were very sensitive to oxygen in the light but were remarkably resistant to oxygen in the dark. When wild-type and mutant cells were subjected to air for various times under dark or light condition, significant decreases in viability were detected in most of the mutants relative to wild type. Treatments with hydrogen peroxide (H(2)O(2)), tert-butyl hydroperoxide (t-BOOH) and methyl viologen resulted in more severe effects in most of the mutants than in the wild type. The results demonstrated that these putative antioxidant proteins combine to form an effective defense against oxygen and reactive oxygen species. Reverse-transcriptase polymerase chain reaction studies showed that the genes with functions in oxidative stress protection were constitutively transcribed under anoxic growth conditions.

  17. Complement-mediated cell death induced by rituximab in B-cell lymphoproliferative disorders is mediated in vitro by a caspase-independent mechanism involving the generation of reactive oxygen species.

    PubMed

    Bellosillo, B; Villamor, N; López-Guillermo, A; Marcé, S; Esteve, J; Campo, E; Colomer, D; Montserrat, E

    2001-11-01

    Mechanisms involving the in vitro effect of rituximab in cells from 55 patients with B-cell lymphoproliferative disorders were investigated. No cytotoxic effect was observed when cells were incubated with rituximab alone, but in the presence of human AB serum rituximab induced complement-dependent cell death (R-CDC). A cytotoxic effect was observed in cells from 9 of 33 patients with B-cell chronic lymphocytic leukemia, 16 of 16 patients with mantle-cell lymphoma, 4 of 4 patients with follicular lymphoma, and 2 of 2 patients with hairy-cell leukemia. R-CDC was observed in cells from patients expressing more than 50 x 10(3) CD20 molecules per cell, and directly correlated with the number of CD20 molecules per cell. Preincubation with anti-CD59 increased the cytotoxic effect of rituximab and sensitized cells from nonsensitive cases. Neither cleavage of poly-ADP ribose polymerase (PARP) nor activation of caspase-3 was observed in R-CDC. In addition, no cells with a hypodiploid DNA content were detected and R-CDC was not prevented by a broad-spectrum caspase inhibitor, suggesting a caspase-independent mechanism. Incubation with rituximab in the presence of AB serum induced a rapid and intense production of reactive oxygen species (ROS). R-CDC was blocked by the incubation of cells with N-acetyl-L-cysteine (NAC) or Tiron, 2 ROS scavengers, indicating that the cytotoxic effect was due to the generation of superoxide (O) radicals. In conclusion, the results of the present study suggest that CD20, CD59, and complement have a role in the in vitro cytotoxic effect of rituximab, which is mediated by a caspase-independent process that involves ROS generation.

  18. Reactive oxygen species in iridium-based OER catalysts.

    PubMed

    Pfeifer, Verena; Jones, Travis E; Wrabetz, Sabine; Massué, Cyriac; Velasco Vélez, Juan J; Arrigo, Rosa; Scherzer, Michael; Piccinin, Simone; Hävecker, Michael; Knop-Gericke, Axel; Schlögl, Robert

    2016-11-18

    Tremendous effort has been devoted towards elucidating the fundamental reasons for the higher activity of hydrated amorphous Ir(III/IV) oxyhydroxides (IrO x ) in the oxygen evolution reaction (OER) in comparison with their crystalline counterpart, rutile-type IrO2, by focusing on the metal oxidation state. Here we demonstrate that, through an analogy to photosystem II, the nature of this reactive species is not solely a property of the metal but is intimately tied to the electronic structure of oxygen. We use a combination of synchrotron-based X-ray photoemission and absorption spectroscopies, ab initio calculations, and microcalorimetry to show that holes in the O 2p states in amorphous IrO x give rise to a weakly bound oxygen that is extremely susceptible to nucleophilic attack, reacting stoichiometrically with CO already at room temperature. As such, we expect this species to play the critical role of the electrophilic oxygen involved in O-O bond formation in the electrocatalytic OER on IrO x . We propose that the dynamic nature of the Ir framework in amorphous IrO x imparts the flexibility in Ir oxidation state required for the formation of this active electrophilic oxygen.

  19. Reactive Oxygen Species are Ubiquitous along Subsurface Redox Gradients

    NASA Astrophysics Data System (ADS)

    Nico, P. S.; Yuan, X.; Davis, J. A.; Dwivedi, D.; Williams, K. H.; Bhattacharyya, A.; Fox, P. M.

    2016-12-01

    Reactive oxygen species (hydroxyl radical, superoxide, hydrogen peroxide, etc.) are known to be important intermediates in many biological and earth system processes. They have been particularly well studied in the realms of atmospheric chemistry and aquatic photochemistry. However, recently there is increasing evidence that they are also present in impactful quantities in dark systems as a result of both biotic and abiotic reactions. Herein we will present a complementary suite of laboratory and field studies examining the presence and production of hydrogen peroxide under relevant subsurface conditions. The laboratory work examines the redox cycling between reduced organic matter, molecular oxygen, and Fe which results in not only the production of hydrogen peroxide and oxidation of organic functional groups but also the maintenance of steady-state concentration of Fe(II) under fully oxygenated aqueous conditions. The field studies involve three distinct locations, namely a shallow subsurface aquifer, a hyporheic zone redox gradient across a river meander, and a hillside shale seep. In all cases detectable quantities (tens of nanomolar) of hydrogen peroxide were measured. In general, concentrations peak under transitional redox conditions where there is the simultaneous presence of reduced Fe, organic matter, and at least trace dissolved oxygen. Many, but not all, of the observed dynamics in hydrogen peroxide production can be reproduced by a simple kinetic model representing the reactions between Fe, organic matter, and molecular oxygen, but many questions remain regarding the role of microorganisms and other redox active chemical species in determining the detected hydrogen peroxide concentrations. The consistent detection of hydrogen peroxide at these disparate locations supports the hypothesis that hydrogen peroxide, and by extension, the entire suite of reactive oxygen species are ubiquitous along subsurface redox gradients.

  20. Physiological roles of mitochondrial reactive oxygen species.

    PubMed

    Sena, Laura A; Chandel, Navdeep S

    2012-10-26

    Historically, mitochondrial reactive oxygen species (mROS) were thought to exclusively cause cellular damage and lack a physiological function. Accumulation of ROS and oxidative damage have been linked to multiple pathologies, including neurodegenerative diseases, diabetes, cancer, and premature aging. Thus, mROS were originally envisioned as a necessary evil of oxidative metabolism, a product of an imperfect system. Yet few biological systems possess such flagrant imperfections, thanks to the persistent optimization of evolution, and it appears that oxidative metabolism is no different. More and more evidence suggests that mROS are critical for healthy cell function. In this Review, we discuss this evidence following some background on the generation and regulation of mROS.

  1. Reactive oxygen species and the cardiovascular system.

    PubMed

    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.

  2. Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway.

    PubMed

    Jo, Guk Heui; Kim, Gi-Young; Kim, Wun-Jae; Park, Kun Young; Choi, Yung Hyun

    2014-10-01

    Sulforaphane, a naturally occurring isothiocyanate found in cruciferous vegetables, has received a great deal of attention because of its ability to inhibit cell proliferation and induce apoptosis in cancer cells. In this study, we investigated the anticancer activity of sulforaphane in the T24 human bladder cancer line, and explored its molecular mechanism of action. Our results showed that treatment with sulforaphane inhibited cell viability and induced apoptosis in T24 cells in a concentration-dependent manner. Sulforaphane-induced apoptosis was associated with mitochondria dysfunction, cytochrome c release and Bcl-2/Bax dysregulation. Furthermore, the increased activity of caspase-9 and -3, but not caspase-8, was accompanied by the cleavage of poly ADP-ribose polymerase, indicating the involvement of the mitochondria-mediated intrinsic apoptotic pathway. Concomitant with these changes, sulforaphane triggered reactive oxygen species (ROS) generation, which, along with the blockage of sulforaphane-induced loss of mitochondrial membrane potential and apoptosis, was strongly attenuated by the ROS scavenger N-acetyl-L-cysteine. Furthermore, sulforaphane was observed to activate endoplasmic reticulum (ER) stress and the nuclear factor-E2-related factor-2 (Nrf2) signaling pathway, as demonstrated by the upregulation of ER stress‑related proteins, including glucose-regulated protein 78 and C/EBP-homologous protein, and the accumulation of phosphorylated Nrf2 proteins in the nucleus and induction of heme oxygenase-1 expression, respectively. Taken together, these results demonstrate that sulforaphane has antitumor effects against bladder cancer cells through an ROS-mediated intrinsic apoptotic pathway, and suggest that ER stress and Nrf2 may represent strategic targets for sulforaphane-induced apoptosis.

  3. Reactive Oxygen Species and Neutrophil Function.

    PubMed

    Winterbourn, Christine C; Kettle, Anthony J; Hampton, Mark B

    2016-06-02

    Neutrophils are essential for killing bacteria and other microorganisms, and they also have a significant role in regulating the inflammatory response. Stimulated neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of superoxide, which acts as a precursor of hydrogen peroxide and other reactive oxygen species that are generated by their heme enzyme myeloperoxidase. When neutrophils engulf bacteria they enclose them in small vesicles (phagosomes) into which superoxide is released by activated NOX2 on the internalized neutrophil membrane. The superoxide dismutates to hydrogen peroxide, which is used by myeloperoxidase to generate other oxidants, including the highly microbicidal species hypochlorous acid. NOX activation occurs at other sites in the cell, where it is considered to have a regulatory function. Neutrophils also release oxidants, which can modify extracellular targets and affect the function of neighboring cells. We discuss the identity and chemical properties of the specific oxidants produced by neutrophils in different situations, and what is known about oxidative mechanisms of microbial killing, inflammatory tissue damage, and signaling.

  4. 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 ...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  6. 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 ...

  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. 15-deoxy-Delta12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription.

    PubMed

    Su, Rong-Ying; Chi, Kwan-Hwa; Huang, Duen-Yi; Tai, Ming-Hui; Lin, Wan-Wan

    2008-10-01

    Although 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) was reported to up-regulate death receptor 5 (DR5) protein expression and sensitize TRAIL-induced cytotoxicity, its action mechanism remains unclear. Using HCT116 colon cancer cells, we found that sensitization of TRAIL-induced cytotoxicity by 15dPGJ(2) resulted from up-regulation of DR5 via gene transcription but was not associated with PPAR-gamma activation. Moreover, 15dPGJ(2) induced GRP78, XBP1, and C/EBP homologous transcription factor (CHOP) expression in HCT116 cells, confirming that 15dPGJ(2) is an endoplasmic reticulum stress inducer. Knockdown of the CHOP gene by siRNA attenuated DR5 up-regulation and the sensitized cytotoxicity in colon cancer HCT116 and SW480. With deletion plasmids of DR5 promoters, we found that the CHOP-binding site was involved in activating the DR5 gene by 15dPGJ(2). A mechanistic study showed the contributions of reactive oxygen species (ROS) and intracellular calcium in CHOP and DR5 gene up-regulation. 15dPGJ(2) was also found to induce DR5 in two prostate cancer cell lines, LNCaP and PC3. Although in LNCaP DR5 up-regulation was accompanied by CHOP expression by 15dPGJ(2), no significant increase in CHOP expression or DR5 promoter activity was observed in PC3 cells. Intriguingly, 15dPGJ(2) induced ROS and calcium production in PC3 cells. This inability to induce CHOP was not due to the p53-null in PC3 cells, as similar extents of increase in CHOP protein were found due to 15dPGJ(2) in both wild-type and p53-null HCT116 cells. In summary, the effect of up-regulation of DR5 by 15dPGJ(2) in colon cancer cells is independent of PPAR-gamma and p53 but relies on CHOP induction through gene transcription involving ROS and calcium.

  9. Nitric oxide and reactive oxygen species in plant biotic interactions.

    PubMed

    Scheler, Claudia; Durner, Jörg; Astier, Jeremy

    2013-08-01

    Nitric oxide (NO) and reactive oxygen species (ROS) are important signaling molecules in plants. Recent progress has been made in defining their role during plant biotic interactions. Over the last decade, their function in disease resistance has been highlighted and focused a lot of investigations. Moreover, NO and ROS have recently emerged as important players of defense responses after herbivore attacks. Besides their role in plant adaptive response development, NO and ROS have been demonstrated to be involved in symbiotic interactions between plants and microorganisms. Here we review recent data concerning these three sides of NO and ROS functions in plant biotic interactions.

  10. [Generation of reactive oxygen species in water under exposure of visible or infrared irradiation at absorption band of molecular oxygen].

    PubMed

    Gudkov, S V; Karp, O E; Garmash, S A; Ivanov, V E; Chernikov, A V; Manokhin, A A; Astashev, M E; Iaguzhinskiĭ, L S; Bruskov, V I

    2012-01-01

    It is found that in bidistilled water saturated with oxygen hydrogen peroxide and hydroxyl radicals are formed under the influence of visible and infrared radiation in the absorption bands of molecular oxygen. Formation of reactive oxygen species (ROS) occurs under the influence of both solar and artificial light sourses, including the coherent laser irradiation. The oxygen effect, i.e. the impact of dissolved oxygen concentration on production of hydrogen peroxide induced by light, is detected. It is shown that the visible and infrared radiation in the absorption bands of molecular oxygen leads to the formation of 8-oxoguanine in DNA in vitro. Physicochemical mechanisms of ROS formation in water when exposed to visible and infrared light are studied, and the involvement of singlet oxygen and superoxide anion radicals in this process is shown.

  11. Indoor particulate reactive oxygen species concentrations.

    PubMed

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

    2014-07-01

    Despite the fact that precursors to reactive oxygen species (ROS) are prevalent indoors, the concentration of ROS inside buildings is unknown. ROS on PM2.5 was measured inside and outside twelve residential buildings and eleven institutional and retail buildings. The mean (± s.d.) concentration of ROS on PM2.5 inside homes (1.37 ± 1.2 nmoles/m(3)) was not significantly different from the outdoor concentration (1.41 ± 1.0 nmoles/m(3)). Similarly, the indoor and outdoor concentrations of ROS on PM2.5 at institutional buildings (1.16 ± 0.38 nmoles/m(3) indoors and 1.68 ± 1.3 nmoles/m(3) outdoors) and retail stores (1.09 ± 0.93 nmoles/m(3) indoors and 1.12 ± 1.1 nmoles/m(3) outdoors) were not significantly different and were comparable to those in residential buildings. The indoor concentration of particulate ROS cannot be predicted based on the measurement of other common indoor pollutants, indicating that it is important to separately assess the concentration of particulate ROS in air quality studies. Daytime indoor occupational and residential exposure to particulate ROS dominates daytime outdoor exposure to particulate ROS. These findings highlight the need for further study of ROS in indoor microenvironments. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Reactive oxygen species and redox compartmentalization.

    PubMed

    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 Ca(2+) 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.

  13. Rooting Responses of Three Oak Species to Low Oxygen Stress

    Treesearch

    Karel A. Jacobs; James D. MacDonald; Alison M. Berry; Laurence R. Costello

    1997-01-01

    Rooting characteristics were compared in blue (Q. douglasii), valley (Q. lobata), and cork oak (Q. suber) seedlings under hypoxic (low oxygen) conditions. A 50 percent reduction in root growth occurred in all species at an oxygen level of 4 percent, or an oxygen diffusion rate of 0.3 mg cm-2...

  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 Tune Root Tropic Responses.

    PubMed

    Krieger, Gat; Shkolnik, Doron; Miller, Gad; Fromm, Hillel

    2016-10-01

    The default growth pattern of primary roots of land plants is directed by gravity. However, roots possess the ability to sense and respond directionally to other chemical and physical stimuli, separately and in combination. Therefore, these root tropic responses must be antagonistic to gravitropism. The role of reactive oxygen species (ROS) in gravitropism of maize and Arabidopsis (Arabidopsis thaliana) roots has been previously described. However, which cellular signals underlie the integration of the different environmental stimuli, which lead to an appropriate root tropic response, is currently unknown. In gravity-responding roots, we observed, by applying the ROS-sensitive fluorescent dye dihydrorhodamine-123 and confocal microscopy, a transient asymmetric ROS distribution, higher at the concave side of the root. The asymmetry, detected at the distal elongation zone, was built in the first 2 h of the gravitropic response and dissipated after another 2 h. In contrast, hydrotropically responding roots show no transient asymmetric distribution of ROS Decreasing ROS levels by applying the antioxidant ascorbate, or the ROS-generation inhibitor diphenylene iodonium attenuated gravitropism while enhancing hydrotropism. Arabidopsis mutants deficient in Ascorbate Peroxidase 1 showed attenuated hydrotropic root bending. Mutants of the root-expressed NADPH oxidase RBOH C, but not rbohD, showed enhanced hydrotropism and less ROS in their roots apices (tested in tissue extracts with Amplex Red). Finally, hydrostimulation prior to gravistimulation attenuated the gravistimulated asymmetric ROS and auxin signals that are required for gravity-directed curvature. We suggest that ROS, presumably H2O2, function in tuning root tropic responses by promoting gravitropism and negatively regulating hydrotropism. © 2016 American Society of Plant Biologists. All Rights Reserved.

  16. Rapid Hydrogen and Oxygen Atom Transfer by a High-Valent Nickel-Oxygen Species.

    PubMed

    Corona, Teresa; Draksharapu, Apparao; Padamati, Sandeep K; Gamba, Ilaria; Martin-Diaconescu, Vlad; Acuña-Parés, Ferran; Browne, Wesley R; Company, Anna

    2016-10-05

    Terminal high-valent metal-oxygen species are key reaction intermediates in the catalytic cycle of both enzymes (e.g., oxygenases) and synthetic oxidation catalysts. While tremendous efforts have been directed toward the characterization of the biologically relevant terminal manganese-oxygen and iron-oxygen species, the corresponding analogues based on late-transition metals such as cobalt, nickel or copper are relatively scarce. This scarcity is in part related to the "Oxo Wall" concept, which predicts that late transition metals cannot support a terminal oxido ligand in a tetragonal environment. Here, the nickel(II) complex (1) of the tetradentate macrocyclic ligand bearing a 2,6-pyridinedicarboxamidate unit is shown to be an effective catalyst in the chlorination and oxidation of C-H bonds with sodium hypochlorite as terminal oxidant in the presence of acetic acid (AcOH). Insight into the active species responsible for the observed reactivity was gained through the study of the reaction of 1 with ClO(-) at low temperature by UV-vis absorption, resonance Raman, EPR, ESI-MS, and XAS analyses. DFT calculations aided the assignment of the trapped chromophoric species (3) as a nickel-hypochlorite species. Despite the fact that the formal oxidation state of the nickel in 3 is +4, experimental and computational analysis indicate that 3 is best formulated as a Ni(III) complex with one unpaired electron delocalized in the ligands surrounding the metal center. Most remarkably, 3 reacts rapidly with a range of substrates including those with strong aliphatic C-H bonds, indicating the direct involvement of 3 in the oxidation/chlorination reactions observed in the 1/ClO(-)/AcOH catalytic system.

  17. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity

    PubMed Central

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  18. Activation mechanism of Gi and Go by reactive oxygen species.

    PubMed

    Nishida, Motohiro; Schey, Kevin L; Takagahara, Shuichi; Kontani, Kenji; Katada, Toshiaki; Urano, Yasuteru; Nagano, Tetsuo; Nagao, Taku; Kurose, Hitoshi

    2002-03-15

    Reactive oxygen species are proposed to work as intracellular mediators. One of their target proteins is the alpha subunit of heterotrimeric GTP-binding proteins (Galpha(i) and Galpha(o)), leading to activation. H(2)O(2) is one of the reactive oxygen species and activates purified Galpha(i2). However, the activation requires the presence of Fe(2+), suggesting that H(2)O(2) is converted to more reactive species such as c*OH. The analysis with mass spectrometry shows that seven cysteine residues (Cys(66), Cys(112), Cys(140), Cys(255), Cys(287), Cys(326), and Cys(352)) of Galpha(i2) are modified by the treatment with *OH. Among these cysteine residues, Cys(66), Cys(112), Cys(140), Cys(255), and Cys(352) are not involved in *OH-induced activation of Galpha(i2). Although the modification of Cys(287) but not Cys(326) is required for subunit dissociation, the modification of both Cys(287) and Cys(326) is necessary for the activation of Galpha(i2) as determined by pertussis toxin-catalyzed ADP-ribosylation, conformation-dependent change of trypsin digestion pattern or guanosine 5'-3-O-(thio)triphosphate binding. Wild type Galpha(i2) but not Cys(287)- or Cys(326)-substituted mutants are activated by UV light, singlet oxygen, superoxide anion, and nitric oxide, indicating that these oxidative stresses activate Galpha(i2) by the mechanism similar to *OH-induced activation. Because Cys(287) exists only in G(i) family, this study explains the selective activation of G(i)/G(o) by oxidative stresses.

  19. Reactive Species Involved in the Regioselective Photooxidation of Heptamethine Cyanines

    PubMed Central

    Nani, Roger R.; Kelley, James A.; Ivanic, Joseph; Schnermann, Martin J.

    2015-01-01

    Heptamethine cyanines are important near-IR fluorophores used in many fluorescence applications. Despite this utility, these molecules are susceptible to light-promoted reactions (photobleaching) involving photochemically generated reactive oxygen species (ROS). Here, we have sought to define key chemical aspects of this nearly inescapable process. Near-IR photolysis of a model heptamethine cyanine leads to the regioselective oxidative cleavage of the cyanine polyene. We report the first quantitative analysis of the major reaction pathway following either photolysis or exposure to candidate ROS. These studies clearly indicate that only singlet oxygen (1O2), and not other feasible ROS, recapitulates the direct photolysis pathway. Computational studies were employed to investigate the regioselectivity of the oxidative cleavage process, and the theoretical ratio is comparable to observed experimental values. These results provide a more complete picture of heptamethine cyanine photooxidation, and provide insight for design of improved compounds for future applications. PMID:26508998

  20. Reactive Species Involved in the Regioselective Photooxidation of Heptamethine Cyanines.

    PubMed

    Nani, Roger R; Kelley, James A; Ivanic, Joseph; Schnermann, Martin J

    2015-11-01

    Heptamethine cyanines are important near-IR fluorophores used in many fluorescence applications. Despite this utility, these molecules are susceptible to light-promoted reactions (photobleaching) involving photochemically generated reactive oxygen species (ROS). Here, we have sought to define key chemical aspects of this nearly inescapable process. Near-IR photolysis of a model heptamethine cyanine leads to the regioselective oxidative cleavage of the cyanine polyene. We report the first quantitative analysis of the major reaction pathway following either photolysis or exposure to candidate ROS. These studies clearly indicate that only singlet oxygen ((1)O2), and not other feasible ROS, recapitulates the direct photolysis pathway. Computational studies were employed to investigate the regioselectivity of the oxidative cleavage process, and the theoretical ratio is comparable to observed experimental values. These results provide a more complete picture of heptamethine cyanine photooxidation, and provide insight for design of improved compounds for future applications.

  1. Shark cartilage-containing preparation: protection against reactive oxygen species.

    PubMed

    Felzenszwalb, I; Pelielo de Mattos, J C; Bernardo-Filho, M; Caldeira-de-Araújo, A

    1998-12-01

    There is overwhelming evidence to indicate that free radicals cause oxidative damage to lipids, proteins and nucleic acids and are involved in the pathogenesis of several degenerative diseases. Therefore, antioxidants, which can neutralize free radicals, may be of central importance in the prevention of these disease states. The protection that fruits and vegetables provide against disease has been attributed to the various antioxidants contained in them. Recently, an anti-inflammatory and analgesic activity of a water-soluble fraction from shark cartilage has been described. Using electrophoretical assays, bacteria survival and transformation and the Salmonella/mammalian-microsome assay, we investigated the putative role of shark cartilage-containing preparation in protecting cells against reactive oxygen species induced DNA damage and mutagenesis. If antimutagens are to have any impact on human disease, it is essential that they are specifically directed against the most common mutagens in daily life. Our data suggest that shark cartilage-containing preparation can play a scavenger role for reactive oxygen species and protects cells against inactivation and mutagenesis.

  2. 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.

  3. 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

  4. 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

  5. The mystery of reactive oxygen species derived from cell respiration.

    PubMed

    Nohl, Hans; Gille, Lars; Staniek, Katrin

    2004-01-01

    Mitochondrial respiration is considered to provide reactive oxygen species (ROS) as byproduct of regular electron transfer. Objections were raised since results obtained with isolated mitochondria are commonly transferred to activities of mitochondria in the living cell. High electrogenic membrane potential was reported to trigger formation of mitochondrial ROS involving complex I and III. Suggested bioenergetic parameters, starting ROS formation, widely change with the isolation mode. ROS detection systems generally applied may be misleading due to possible interactions with membrane constituents or electron carriers. Avoiding these problems no conditions reported to transform mitochondrial respiration to a radical source were confirmed. However, changing the physical membrane state affected the highly susceptible interaction of the ubiquinol/bc(1) redox complex such that ROS formation became possible.

  6. Reactive oxygen species production by catechol stabilized copper nanoparticles.

    PubMed

    Chen, Cheng; Ahmed, Ishtiaq; Fruk, Ljiljana

    2013-12-07

    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.

  7. Reactive oxygen species and the free radical theory of aging.

    PubMed

    Liochev, Stefan I

    2013-07-01

    The traditional view in the field of free radical biology is that free radicals and reactive oxygen species (ROS) are toxic, mostly owing to direct damage of sensitive and biologically significant targets, and are thus a major cause of oxidative stress; that complex enzymatic and nonenzymatic systems act in concert to counteract this toxicity; and that a major protective role is played by the phenomenon of adaptation. Another part of the traditional view is that the process of aging is at least partly due to accumulated damage done by these harmful species. However, recent workers in this and in related fields are exploring the view that superoxide radical and reactive oxygen species exert beneficial effects. Thus, such ROS are viewed as involved in cellular regulation by acting as (redox) signals, and their harmful effects are seen mostly as a result of compromised signaling, rather than due to direct damage to sensitive targets. According to some followers of this view, ROS such as hydrogen peroxide and superoxide are not just causative agents of aging but may also be agents that increase the life span by acting, for example, as prosurvival signals. The goal of this review is to recall that many of the effects of ROS that are interpreted as beneficial may actually represent adaptations to toxicity and that some of the most extravagant recent claims may be due to misinterpretation, oversimplification, and ignoring the wealth of knowledge supporting the traditional view. Whether it is time to abandon the free radical (oxidative stress) theory of aging is considered. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Reactive oxygen species induce apoptosis in bronchial epithelial BEAS-2B cells by inhibiting the antiglycation glyoxalase I defence: involvement of superoxide anion, hydrogen peroxide and NF-κB.

    PubMed

    Antognelli, Cinzia; Gambelunghe, Angela; Talesa, Vincenzo Nicola; Muzi, Giacomo

    2014-01-01

    Reactive oxygen species (ROS) are implicated in the regulation of apoptosis through a number of distinct mechanisms depending on cell type and stimulation conditions. Glyoxalase I (GI) metabolizes methylglyoxal (MG) and MG-derived advanced glycation end products (AGEs) known to cause apoptosis. This study examined the possible role of GI among the mechanisms of ROS-driven apoptosis in human bronchial epithelial BEAS-2B cells exposed to wood dust and signaling pathways by which these reactive species regulate GI expression. Our results showed that wood dust generated distinct ROS (superoxide anion, and hydrogen peroxide) by selectively inhibiting the enzymatic activity of superoxide dismutase or glutathione peroxidase and catalase enzymes. These ROS caused a dramatic inhibition of the antiglycation GI enzyme, leading to the intracellular accumulation of the pro-apoptotic AGE, argpyrimidine (AP) and programmed cell death via a mitochondrial pathway. Pre-treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, prevented these events. Hence, ROS-induced apoptosis in BEAS-2B cells occurred via a novel mechanism relying on GI inhibition and AP accumulation. We interestingly found that superoxide anion and hydrogen peroxide induced a diverse apoptosis level by differently inhibiting GI via NF-κB pathway. Since maintenance of an intact epithelium is a critically important determinant of normal respiratory function, the knowledge of the mechanisms underlying its disruption may provide insight into the genesis of a number of pathological conditions commonly occurring in wood dust occupational exposure. Our findings suggest that the antioxidant NAC may merit investigation as a potential preventive agent in wood dust exposure-induced respiratory diseases.

  9. [Formation of reactive oxygen species during pollen grain germination].

    PubMed

    Smirnova, A V; Matveeva, N P; Polesskaia, O G; Ermakov, I P

    2009-01-01

    The formation of reactive oxygen species in pollen at the early germination stage, which precedes the formation of the pollen tube, was studied. During this period, pollen grain is being hydrated, abruptly increasing its volume, and it passes from the resting state to active metabolism. Fluorescent methods have made it possible to reveal reactive oxygen species in the cytoplasm and inner layer of the pollen wall, intine. The cytoplasmic reactive oxygen species were mostly found in mitochondria, while extracellular ones were localized in aperture zones of intine, as well as in the solution surrounding pollen grains in vitro. The content of extracellular reactive oxygen species decreased after superoxide dismutase (100 units per ml) and diphenylene iodonium (100 microM), which indicates NADPH oxidase as one of possible producent of them. In conditions of suppression of extracellular reactive oxygen species production (100 microM diphenilene iodonium) or their promoted removal (after addition of 10 to 100 microM ascorbic acid), the number of germinating pollen grains increased. This effect disappeared after further increase in the concentration of the listed reagents. The result is evidence of the significance of processes of generation/removal of extracellular reactive oxygen species for pollen germination.

  10. Genotoxicity of volatile and secondary reactive oxygen species generated by photosensitization

    SciTech Connect

    Camoirano, A.; De Flora, S.; Dahl, T.A. Tufts Univ. Veterinary, Boston, MA )

    1993-01-01

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

  11. 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.

  12. Reactive Oxygen Species: A Key Hallmark of Cardiovascular Disease

    PubMed Central

    2016-01-01

    Cardiovascular diseases (CVDs) have been the prime cause of mortality worldwide for decades. However, the underlying mechanism of their pathogenesis is not fully clear yet. It has been already established that reactive oxygen species (ROS) play a vital role in the progression of CVDs. ROS are chemically unstable reactive free radicals containing oxygen, normally produced by xanthine oxidase, nicotinamide adenine dinucleotide phosphate oxidase, lipoxygenases, or mitochondria or due to the uncoupling of nitric oxide synthase in vascular cells. When the equilibrium between production of free radicals and antioxidant capacity of human physiology gets altered due to several pathophysiological conditions, oxidative stress is induced, which in turn leads to tissue injury. This review focuses on pathways behind the production of ROS, its involvement in various intracellular signaling cascades leading to several cardiovascular disorders (endothelial dysfunction, ischemia-reperfusion, and atherosclerosis), methods for its detection, and therapeutic strategies for treatment of CVDs targeting the sources of ROS. The information generated by this review aims to provide updated insights into the understanding of the mechanisms behind cardiovascular complications mediated by ROS. PMID:27774507

  13. Reactive oxygen species in programmed death of pea guard cells.

    PubMed

    Samuilov, V D; Kiselevsky, D B; Shestak, A A; Nesov, A V; Vasil'ev, L A

    2008-10-01

    Hydrogen peroxide potentiates CN(-)-induced apoptosis of guard cells recorded as destruction of cell nuclei in the epidermis from pea leaves. A still stronger effect was exerted by the addition of H2O2 and NADH, which are the substrates of the plant cell wall peroxidase producing O2*- coupled to the oxidation of NADH. The CN(-)-or (CN(-) + H2O2)-induced destruction of guard cell nuclei was completely removed by nitroblue tetrazolium (NBT) oxidizing O2*- and preventing there-by the subsequent generation of H2O2. The reduced NBT was deposited in the cells as formazan crystals. Cyanide-induced apoptosis was diminished by mannitol and ethanol, which are OH* traps. The dyes Rose Bengal (RB) and tetramethylrhodamine ethyl ester (TMRE) photosensitizing singlet oxygen production suppressed the CN(-)-induced destruction of the cell nuclei in the light. This suppression was removed by exogenous NADH, which reacts with 1O2 yielding O2*-. Incubation of leaf slices with RB in the light lowered the photosynthetic O2 evolution rate and induced the permeability of guard cells for propidium iodide, which cannot pass across intact membranes. Inhibition of photosynthetic O2 evolution by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea or bromoxynil prevented CN(-)-induced apoptosis of guard cells in the light but not in the dark. RB in combination with exogenous NADH caused H2O2 production that was sensitive to NBT and estimated from dichlorofluorescein (DCF) fluorescence. Data on NBT reduction and DCF and TMRE fluorescence obtained using a confocal microscope and data on the NADH-dependent H2O2 production are indicative of generation of reactive oxygen species in the chloroplasts, mitochondria, and nuclear region of guard cells as well as with participation of apoplastic peroxidase. Cyanide inhibited generation of reactive oxygen species in mitochondria and induced their generation in chloroplasts. The results show that H2O2, OH*, and O2*- resources utilized for H2O2 production are

  14. Reactive oxygen species induce procalcitonin expression in trigeminal ganglia glia

    PubMed Central

    Raddant, Ann C.; Russo, Andrew F.

    2014-01-01

    Objective To examine calcitonin gene-related peptide (CGRP) gene expression under inflammatory conditions using trigeminal ganglia organ cultures as an experimental system. These cultures have increased proinflammatory signaling that may mimic neurogenic inflammation in the migraine state. Background The trigeminal nerve sends peripheral pain signals to the central nervous system during migraine. Understanding the dynamic processes that occur within the trigeminal nerve and ganglion may provide insights into events that contribute to migraine pain. A neuropeptide of particular interest is CGRP, which can be elevated and play a causal role in migraine. However, most studies have overlooked a second splice product of the CALCA gene, which encodes calcitonin (CT), a peptide hormone involved in calcium homeostasis. Importantly, a precursor form of calcitonin called procalcitonin (proCT) can act as a partial agonist at the CGRP receptor and elevated proCT has recently been reported during migraine. Methods We used a trigeminal ganglion whole organ explant model, which has previously been demonstrated to induce pro-inflammatory agents in vitro. Quantitative PCR and immunohistochemistry were used to evaluate changes in mRNA and protein levels of CGRP and proCT. Results Whole mouse trigeminal ganglia cultured for 24 h showed a 10-fold increase in CT mRNA, with no change in CGRP mRNA. A similar effect was observed in ganglia from adult rats. ProCT immunoreactivity was localized in glial cells. Cutting the tissue blunted the increase in CT, suggesting that induction required the close environment of the intact ganglia. Consistent with this prediction, there were increased reactive oxygen species in the ganglia and the elevated CT mRNA was reduced by antioxidant treatment. Surprisingly, reactive oxygen species were increased in neurons, not glia. Conclusions These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal

  15. Generation of reactive oxygen species by the faecal matrix

    PubMed Central

    Owen, R; Spiegelhalder, B; Bartsch, H

    2000-01-01

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


Keywords: colorectal cancer; faecal matrix; hypoxanthine; phytic acid; reactive oxygen species; xanthine oxidase PMID:10644317

  16. Globular adiponectin inhibits ethanol-induced reactive oxygen species production through modulation of NADPH oxidase in macrophages: involvement of liver kinase B1/AMP-activated protein kinase pathway.

    PubMed

    Kim, Mi Jin; Nagy, Laura E; Park, Pil-Hoon

    2014-09-01

    Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown to play protective roles against chronic alcohol consumption. Although excessive reactive oxygen species (ROS) production in macrophages is considered one of the critical events for ethanol-induced damage in various target tissues, the effect of adiponectin on ethanol-induced ROS production is not clearly understood. In the present study, we investigated the effect of globular adiponectin (gAcrp) on ethanol-induced ROS production and the potential mechanisms underlying these effects of gAcrp in macrophages. Here we demonstrated that gAcrp prevented ethanol-induced ROS production in both RAW 264.7 macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced increase in the expression of NADPH oxidase subunits, including Nox2 and p22(phox), via modulation of nuclear factor-κB pathway. Furthermore, pretreatment with compound C, a selective inhibitor of AMPK, or knockdown of AMPK by small interfering RNA restored suppression of ethanol-induced ROS production and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2 expression, suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and activation of NADPH oxidase by gAcrp. Taken together, these results demonstrate that globular adiponectin prevents ethanol-induced ROS production, at least in part, via modulation of NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in the suppression of ethanol-induced NADPH oxidase activation by gAcrp in macrophages.

  17. ITN1, a novel gene encoding an ankyrin-repeat protein that affects the ABA-mediated production of reactive oxygen species and is involved in salt-stress tolerance in Arabidopsis thaliana.

    PubMed

    Sakamoto, Hikaru; Matsuda, Osamu; Iba, Koh

    2008-11-01

    Salt stress and abscisic acid (ABA) induce accumulation of reactive oxygen species (ROS) in plant cells. ROS not only act as second messengers for the activation of salt-stress responses, but also have deleterious effects on plant growth due to their cytotoxicity. Therefore, the timing and degree of activation of ROS-producing or ROS-scavenging enzymes must be tightly regulated under salt-stress conditions. We identified a novel locus of Arabidopsis, designated itn1 (increased tolerance to NaCl1), whose disruption leads to increased salt-stress tolerance in vegetative tissues. ITN1 encodes a transmembrane protein with an ankyrin-repeat motif that has been implicated in diverse cellular processes such as signal transduction. Comparative microarray analysis between wild-type and the itn1 mutant revealed that induction of genes encoding the ROS-producing NADPH oxidases (RBOHC and RBOHD) under salt-stress conditions was suppressed in the mutant. This suppression was accompanied by a corresponding reduction in ROS accumulation. The ABA-induced expression of RBOHC and RBOHD was also suppressed in the mutant, as was the case for RD29A, an ABA-inducible marker gene. However, the ABA-induced expression of another marker gene, RD22, was not impaired in the mutant. These results suggest that the itn1 mutation partially impairs ABA signaling pathways, possibly leading to the reduction in ROS accumulation under salt-stress conditions. We discuss the possible mechanisms underlying the salt-tolerant phenotype of the itn1 mutant.

  18. Role of reactive oxygen species in fungal cellular differentiations.

    PubMed

    Scott, Barry; Eaton, Carla J

    2008-12-01

    Regulated synthesis of reactive oxygen species (ROS) by specific fungal NADPH oxidases (Noxs) plays a key role in fungal cellular differentiation and development. Fungi have up to three different Nox isoforms, NoxA, B and C. The NoxA isoform has a key role in triggering the development of fruiting bodies in several sexual species whereas NoxB plays a key role in ascospore germination. The function of NoxC remains unknown. Both NoxA and NoxB are required for the development of fungal infection structures by some plant pathogens. ROS production by NoxA is critical for maintaining a fungal-plant symbiosis. Localised synthesis of ROS is also important in establishing and maintaining polarised hyphal growth. Activation of NoxA/NoxB requires the regulatory subunit, NoxR, and the small GTPase RacA. The BemA scaffold protein may also be involved in the assembly of the Nox complex. By analogy with mammalian systems MAP and PAK kinases may regulate fungal Nox activation. How fungal cells sense and respond to ROS associated with cellular differentiations remains to be discovered.

  19. Radical Oxygen Species, Exercise and Aging: An Update.

    PubMed

    Bouzid, Mohamed Amine; Filaire, Edith; McCall, Alan; Fabre, Claudine

    2015-09-01

    It is now well established that reactive oxygen species (ROS) play a dual role as both deleterious and beneficial species. In fact, ROS act as secondary messengers in intracellular signalling cascades; however, they can also induce cellular senescence and apoptosis. Aging is an intricate phenomenon characterized by a progressive decline in physiological functions and an increase in mortality, which is often accompanied by many pathological diseases. ROS are involved in age-associated damage to macromolecules, and this may cause derangement in ROS-mediated cell signalling, resulting in stress and diseases. Moreover, the role of oxidative stress in age-related sarcopenia provides strong evidence for the important contribution of physical activity to limit this process. Regular physical activity is considered a preventive measure against oxidative stress-related diseases. The aim of this review is to summarize the currently available studies investigating the effects of chronic and/or acute physical exercise on the oxidative stress process in healthy elderly subjects. Although studies on oxidative stress and physical activity are limited, the available information shows that acute exercise increases ROS production and oxidative stress damage in older adults, whereas chronic exercise could protect elderly subjects from oxidative stress damage and reinforce their antioxidant defences. The available studies reveal that to promote beneficial effects of physical activity on oxidative stress, elderly subjects require moderate-intensity training rather than high-intensity exercise.

  20. Reactive oxygen species and vascular biology: implications in human hypertension.

    PubMed

    Touyz, Rhian M; Briones, Ana M

    2011-01-01

    Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

  1. Mechanism of teratogenesis: electron transfer, reactive oxygen species, and antioxidants.

    PubMed

    Kovacic, Peter; Somanathan, Ratnasamy

    2006-12-01

    Teratogenesis has been a topic of increasing interest and concern in recent years, generating controversy in association with danger to humans and other living things. A veritable host of chemicals is known to be involved, encompassing a wide variety of classes, both organic and inorganic. Contact with these chemicals is virtually unavoidable due to contamination of air, water, ground, food, beverages, and household items, as well as exposure to medicinals. The resulting adverse effects on reproduction are numerous. There is uncertainty regarding the mode of action of these chemicals, although various theories have been advanced, e.g., disruption of the central nervous system (CNS), DNA attack, enzyme inhibition, interference with hormonal action, and insult to membranes, proteins, and mitochondria. This review provides extensive evidence for involvement of oxidative stress (OS) and electron transfer (ET) as a unifying theme. Successful application of the mechanistic approach is made to all of the main classes of toxins, in addition to large numbers of miscellaneous types. We believe it is not coincidental that the vast majority of these substances incorporate ET functionalities (quinone, metal complex, ArNO2, or conjugated iminium) either per se or in metabolites, potentially giving rise to reactive oxygen species (ROS) by redox cycling. Some categories, e.g., peroxides and radiation, appear to generate ROS by non-ET routes. Other mechanisms are briefly addressed; a multifaceted approach to mode of action appears to be the most logical. Our framework should increase understanding and contribute to preventative measures, such as use of antioxidants.

  2. 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Reactive oxygen species mediate lethality induced by far-UV in Escherichia coli cells.

    PubMed

    Gomes, A A; Silva-Júnior, A C T; Oliveira, E B; Asad, L M B O; Reis, N C S C; Felzenszwalb, I; Kovary, K; Asad, N R

    2005-01-01

    The involvement of reactive oxygen species (ROS) in the induction of DNA damage to Escherichia coli cells caused by UVC (254 nm) irradiation was studied. We verified the expression of the soxS gene induced by UVC (254 nm) and its inhibition by sodium azide, a singlet oxygen (1O2) scavenger. Additional results showed that a water-soluble carotenoid (norbixin) protects against the lethal effects of UVC. These results suggest that UVC radiation can also cause ROS-mediated lethality.

  4. Threshold electron attachment and electron impact ionization involving oxygen dimers

    NASA Astrophysics Data System (ADS)

    Kreil, J.; Ruf, M.-W.; Hotop, H.; Ettischer, I.; Buck, U.

    1998-12-01

    Using two different crossed-beams machines we have carried out the first quantitative study of threshold electron attachment and electron impact-induced ionization and fragmentation involving oxygen dimers (O 2) 2. In the electron attachment experiment we study electron transfer from state-selected Ar **(20d) Rydberg atoms to O 2 molecules and dimers in a skimmed supersonic beam at variable nozzle temperatures ( T0) and stagnation pressures ( p0). The relative dimer density is determined through measurements of Penning ionization by metastable Ne *(3s 3P2,0) atoms and used to estimate the absolute cross-section for O 2- formation in collisions of Ar **(20d) Rydberg atoms with O 2 dimers to be nearly 10 -17 m 2, almost four orders of magnitude larger than that for O 2- formation in collisions of Ar **(20d) Rydberg atoms with O 2 monomers. The fragmentation of the oxygen cluster beam is quantitatively characterized by the transverse helium beam scattering method which allows us to spatially separate different clusters. It is shown that in 70 eV electron impact of (O 2) 2 only 3.6(4)% of the dimers are detected as dimer ions (O 2) 2+. In additional experiments involving SF 6 clusters we show that SF 6 dimers fragment nearly completely upon 70 eV electron impact, yielding SF 5+ ions (probability for (SF 6)·SF 5+ production at most 0.3%).

  5. 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.

  6. 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

  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. Kinetics of oxygen species in an electrically driven singlet oxygen generator

    NASA Astrophysics Data System (ADS)

    Azyazov, V. N.; Torbin, A. P.; Pershin, A. A.; Mikheyev, P. A.; Heaven, M. C.

    2015-12-01

    The kinetics of oxygen species in the gaseous medium of a discharge singlet oxygen generator has been revisited. Vibrationally excited ozone O3(υ) formed in O + O2 recombination is thought to be a significant agent in the deactivation of singlet oxygen O2(a1Δ), oxygen atom removal and ozone formation. It is shown that the process O3(υ ⩾ 2) + O2(a1Δ) → 2O2 + O is the main O2(a1Δ) deactivation channel in the post-discharge zone. If no measures are taken to decrease the oxygen atom concentration, the contribution of this process to the overall O2(a1Δ) removal is significant, even in the discharge zone. A simplified model for the kinetics of vibrationally excited ozone is proposed. Calculations based on this model yield results that are in good agreement with the experimental data.

  9. 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. Copyright © 2016 the American Physiological Society.

  10. 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.

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

    PubMed Central

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

    2015-01-01

    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

  12. 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.

  13. Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling

    PubMed Central

    2014-01-01

    Background Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. Results In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Conclusions Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling. PMID:24898702

  14. 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

  15. Formation of protein S-nitrosylation by reactive oxygen species.

    PubMed

    Hlaing, K Htet; Clément, M-V

    2014-09-01

    In the present study, the formation of whole cellular S-nitrosylated proteins (protein-SNOs) by the reactive oxygen species (ROS), hydrogen peroxide (H2O2), and superoxide (O2(•-)) is demonstrated. A spectrum of protein cysteine oxidative modifications was detected upon incubation of serum-starved mouse embryonic fibroblasts with increasing concentrations of exogenous H2O2, ranging from exclusive protein-SNOs at low concentrations to a mixture of protein-SNOs and other protein oxidation at higher concentrations to exclusively non-SNO protein oxidation at the highest concentrations of the oxidant used. Furthermore, formation of protein-SNOs was also detected upon inhibition of the antioxidant protein Cu/Zn superoxide dismutase that results in an increase in intracellular concentration of O2(•-). These results were further validated using the phosphatase and tensin homologue, PTEN, as a model of a protein sensitive to oxidative modifications. The formation of protein-SNOs by H2O2 and O2(•-) was prevented by the NO scavenger, c-PTIO, as well as the peroxinitrite decomposition catalyst, FETPPS, and correlated with the production or the consumption of nitric oxide (NO), respectively. These data suggest that the formation of protein-SNOs by H2O2 or O2(•-) requires the presence or the production of NO and involves the formation of the nitrosylating intermediate, peroxinitrite.

  16. Reactive oxygen species in phytopathogenic fungi: signaling, development, and disease.

    PubMed

    Heller, Jens; Tudzynski, Paul

    2011-01-01

    Reactive oxygen species (ROS) play a major role in pathogen-plant interactions: recognition of a pathogen by the plant rapidly triggers the oxidative burst, which is necessary for further defense reactions. The specific role of ROS in pathogen defense is still unclear. Studies on the pathogen so far have focused on the importance of the oxidative stress response (OSR) systems to overcome the oxidative burst or of its avoidance by effectors. This review focuses on the role of ROS for fungal virulence and development. In the recent years, it has become obvious that (a) fungal OSR systems might not have the predicted crucial role in pathogenicity, (b) fungal pathogens, especially necrotrophs, can actively contribute to the ROS level in planta and even take advantage of the host's response, (c) fungi possess superoxide-generating NADPH oxidases similar to mammalian Nox complexes that are important for pathogenicity; however, recent data indicate that they are not directly involved in pathogen-host communication but in fungal differentiation processes that are necessary for virulence. Copyright © 2011 by Annual Reviews. All rights reserved.

  17. 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...

  18. 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...

  19. 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.

  20. 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.

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

    PubMed

    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(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.

  2. 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.

  3. 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

  4. Hydrazide derivatives produce active oxygen species as hydrazine.

    PubMed

    Timperio, Anna Maria; Rinalducci, Sara; Zolla, Lello

    2005-12-01

    It is well documented that some hydrazines are quite sensitive to oxidation and may serve as the electron donor for the reduction of oxygen, whereas hydrazides are not believed to react directly with oxygen. Data presented in this paper show that both hydrazides and hydrazines share an N-N moiety, which is assumed to react with atmospheric oxygen and produce oxygen radicals, at various degrees of efficiency. Since spectrometric measurements of hydrazide just after solubilization showed that the molecular mass remains constant in the absence of oxygen, we can conclude that hydrazides do not react with the oxygen through a slow spontaneous hydrolytic release of hydrazine. However, hydrazine is more reactive than hydrazide, which requires hours rather than minutes to produce measurable quantities of radical species. Differences were also apparent for various substituted derivatives. The reaction was significantly enhanced by the presence of metal ions. Data reported here demonstrate that hydrazides cause irreversible damage to the prosthetic group of proteins as well as causing degradation of the polypeptide chain into small fragments.

  5. Chemical Recognition of Active Oxygen Species on the Surface of Oxygen Evolution Reaction Electrocatalysts.

    PubMed

    Yang, Chunzhen; Fontaine, Olivier; Tarascon, Jean-Marie; Grimaud, Alexis

    2017-07-17

    Owing to the transient nature of the intermediates formed during the oxygen evolution reaction (OER) on the surface of transition metal oxides, their nature remains largely elusive by the means of simple techniques. The use of chemical probes is proposed, which, owing to their specific affinities towards different oxygen species, unravel the role played by these species on the OER mechanism. For that, tetraalkylammonium (TAA) cations, previously known for their surfactant properties, are introduced, which interact with the active oxygen sites and modify the hydrogen bond network on the surface of OER catalysts. Combining chemical probes with isotopic and pH-dependent measurements, it is further demonstrated that the introduction of iron into amorphous Ni oxyhydroxide films used as model catalysts deeply modifies the proton exchange properties, and therefore the OER mechanism and activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 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

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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

  12. The influence of reactive oxygen species on local redox conditions in oxygenated natural waters

    NASA Astrophysics Data System (ADS)

    Rose, Andrew

    2016-11-01

    Redox conditions in natural waters are a fundamental control on biogeochemical processes and ultimately many ecosystem functions. While the dioxygen/water redox couple controls redox thermodynamics in oxygenated aquatic environments on geological timescales, it is kinetically inert in the extracellular environment on the much shorter timescales on which many biogeochemical processes occur. Instead, electron transfer processes on these timescales are primarily mediated by a relatively small group of trace metals and stable radicals, including the reactive oxygen species superoxide. Such processes are of critical biogeochemical importance because many of these chemical species are scarce nutrients, but may also be toxic at high concentrations. Furthermore, their bioavailability and potentially toxicity is typically strongly influenced by their redox state. In this paper, I examine to what extent redox conditions in oxygenated natural waters are expected to be reflected in the redox states of labile redox-active compounds that readily exchange electrons with the dioxygen/superoxide redox couple, and potentially with each other. Additionally, I present the hypothesis that that the relative importance of the dioxygen/superoxide and superoxide/hydrogen peroxide redox couples exerts a governing control on local redox conditions in oxygenated natural waters on biogeochemically important timescales. Given the recent discovery of widespread extracellular superoxide production by a diverse range of organisms, this suggests the existence of a fundamental mechanism for organisms to tightly regulate local redox conditions in their extracellular environment in oxygenated natural waters.

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

    PubMed

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

    2008-08-01

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

  14. Reactive oxygen species signaling in plants under abiotic stress.

    PubMed

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

    2013-04-01

    Abiotic stresses like heavy metals, drought, salt, low temperature, etc. are the major factors that limit crop productivity and yield. These stresses are associated with production of certain deleterious chemical entities called reactive oxygen species (ROS), which include hydrogen peroxide (H₂O₂), superoxide radical (O₂(-)), hydroxyl radical (OH(-)), etc. ROS are capable of inducing cellular damage by degradation of proteins, inactivation of enzymes, alterations in the gene and interfere in various pathways of metabolic importance. Our understanding on ROS in response to abiotic stress is revolutionized with the advancements in plant molecular biology, where the basic understanding on chemical behavior of ROS is better understood. Understanding the molecular mechanisms involved in ROS generation and its potential role during abiotic stress is important to identify means by which plant growth and metabolism can be regulated under acute stress conditions. ROS mediated oxidative stress, which is the key to understand stress related toxicity have been widely studied in many plants and the results in those studies clearly revealed that oxidative stress is the main symptom of toxicity. Plants have their own antioxidant defense mechanisms to encounter ROS that is of enzymic and non-enzymic nature . Coordinated activities of these antioxidants regulate ROS detoxification and reduces oxidative load in plants. Though ROS are always regarded to impart negative impact on plants, some reports consider them to be important in regulating key cellular functions; however, such reports in plant are limited. Molecular approaches to understand ROS metabolism and signaling have opened new avenues to comprehend its critical role in abiotic stress. ROS also acts as secondary messenger that signals key cellular functions like cell proliferation, apoptosis and necrosis. In higher eukaryotes, ROS signaling is not fully understood. In this review we summarize our understanding on ROS

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

    PubMed

    Lushchak, Volodymyr I

    2014-12-05

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

  16. Multi-species simulation of Trichel pulses in oxygen

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  17. Quantification of reactive oxygen species for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Tan, Zou; Zhang, Jinde; Lin, Lisheng; Li, Buhong

    2016-10-01

    Photodynamic therapy (PDT) is an effective therapeutic modality that uses a light source to activate light-sensitive photosensitizers to treat both oncologic and nononcological indications. Photosensitizers are excited to the long-lived triplet state, and they react with biomolecules via type I or II mechanism resulted in cell death and tumor necrosis. Free radicals and radical ions are formed by electron transfer reactions (type I), which rapidly react with oxygen leading to the production of reactive oxygen species (ROS), including superoxide ions, hydroxyl radicals and hydrogen peroxide. Singlet molecular oxygen is produced in a Type II reaction, in which the excited singlet state of the photosensitizer generated upon photon absorption by the ground-state photosensitizer molecule undergoes intersystem crossing to a long-lived triplet state. In this talk, the fundmental mechanisms and detection techniques for ROS generation in PDT will be introduced. In particular, the quantification of singlet oxygen generation for pre-clinical application will be highlighted, which plays an essential role in the establishment of robust singlet oxygen-mediated PDT dosimetry.

  18. KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species

    PubMed Central

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

    2010-01-01

    KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the

  19. KRIT1 regulates the homeostasis of intracellular reactive oxygen species.

    PubMed

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

    2010-07-26

    KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1(-/-) cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1(-/-) cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45alpha, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the cell

  20. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis.

    PubMed

    Khan, Saeed R

    2014-09-01

    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

  1. 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

    2012-07-03

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

  2. 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.

  3. 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.

  4. 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.

  5. Reactive oxygen species produced from chromate pigments and ascorbate.

    PubMed Central

    Lefebvre, Y; Pezerat, H

    1994-01-01

    The reactions of various chromate pigments and ascorbate were investigated by an ESR spin trapping technique. Production of Cr(V) was detected directly and productions of very electrophilic reactive oxygen species (ROS) was detected via the oxidation of formate. We demonstrated previously that both dissolved oxygen and Cr (V) were essential in the production of ROS in this system, and that ROS production was inhibited by catalase. We studied here the effect of solubility of different chromate pigments: sodium, calcium, strontium, basic zinc, basic lead supported on silica, and lead and barium chromates on the production of ROS in buffered medium and cell culture medium (Dublecco's Modified Eagle medium + fetal calf serum). Sodium, calcium, basic zinc, and basic lead chromates were active in the production of ROS in presence of cell culture medium, whereas lead and barium chromates were inactive. PMID:7843106

  6. On reactive oxygen species measurement in living systems.

    PubMed

    Pavelescu, L A

    2015-01-01

    Studies devoted to the detection and measurement of free radicals in biological systems generally generated accepted methods of reactive oxygen species (ROS) level analysis. When out of control, ROS induces tissue damage, chronic inflammatory processes and cellular functional disturbances. Aerobic organisms have adapted to defense against ROS aggression by developing potent antioxidant mechanisms. Recent advances in ROS measurement methodology allow the study of ROS biology at a previously unachievable level of precision. However, their high activity, very short life span and extremely low concentration, make ROS measurement a challenging subject for researchers.

  7. 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

  8. Manganese neurotoxicity and the role of reactive oxygen species.

    PubMed

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

    2013-09-01

    Manganese (Mn) is an essential dietary nutrient, but an excess or accumulation can be toxic. Disease states, such as 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 providing an overview of the absorption, distribution, and excretion of Mn and the stability and transport of Mn compounds in the body.

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

    NASA Astrophysics Data System (ADS)

    Mai, Trang; Hilt, J. Zach

    2017-07-01

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

  10. Reactive oxygen species in regulation of fungal development.

    PubMed

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

    2007-10-01

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

  11. Reactive oxygen species mediate phorbol ester-stimulated cAMP response in human eosinophils.

    PubMed

    Ezeamuzie, Charles I; Taslim, Najla

    2006-08-14

    Recently, we showed that phorbol 12-myristate 13-acetate (PMA) can cause a direct, PKC-dependent, stimulation of intracellular cAMP in human eosinophils. Since PMA also stimulates the release of reactive oxygen species in these cells, we have investigated whether reactive oxygen species are involved in the cAMP response. Provided eosinophils were incubated for <20 min at 37 degrees C before stimulation, PMA potently stimulated cAMP generation that surpassed that of histamine. Pre-treatment of the cells with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI) and apocynin, strongly inhibited the cAMP production induced by PMA, but not that induced by histamine. This treatment also strongly inhibited the release of superoxide anions (O(2)(-)). The cAMP response was also inhibited by pre-treatment with the specific peroxide scavenger, ebselen, but not superoxide dismutase, or NG-nitro-l-arginine methyl ester (L-NAME), thus, suggesting the possible involvement of a peroxide rather than O(2)(-) or nitric oxide (NO). These results reveal a novel involvement of intracellular reactive oxygen species in protein kinase C (PKC)-dependent stimulation of cAMP production in human eosinophils.

  12. Extracellular Production of Reactive Oxygen Species by Marine Microbiota

    NASA Astrophysics Data System (ADS)

    Schneider, R. J.; Roe, K. L.; Voelker, B. M.; Hansel, C. M.

    2016-02-01

    The reactive oxygen species (ROS) superoxide (O2-) and hydrogen peroxide (H2O2) are important to the cycling of trace metals and carbon in marine systems. Previous studies have shown that biological ROS production in the ocean may be significant. We examined the ability of five common species of diatoms to produce and break down ROS in the presence and absence of light by suspending cells on filters and measuring downstream ROS concentrations using chemiluminescence probes. Results show a wide range of rates (undetectable to 7.3 x 10-16 mol cell-1 hr-1) and suggest that extracellular ROS production occurs through a variety of pathways. H2O2 decay appears to be mediated primarily by active cell processes, while O2- appears to occur through a combination of active and passive cell processes. Extracellular H2O2 production and decay were also determined for twelve species of heterotrophic bacteria using two different methodologies. Measured decay rates were consistent despite methodological differences. By contrast, large variability of production rates was observed could vary significantly even among between replicates of the same species measured using the same methodology. Although production rates cannot be stated with certainty, it is likely that extracellular H2O2 production occurs in most bacterial species.

  13. In situ reactive oxygen species production for tertiary wastewater treatment.

    PubMed

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

    2015-05-01

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

  14. 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.

  15. 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

  16. Myoglobin oxygenation and autoxidation in three reptilian species.

    PubMed

    Helbo, Signe; Bundgaard, Amanda G; Fago, Angela

    2015-09-01

    Differences between species in the oxygen (O2) affinity (P50) of myoglobin (Mb) may serve to fine tune O2 supply to cardiac and skeletal muscle in ectotherms. In support of this view, it has been shown that fish Mb O2 affinities differ between species when measured at the same temperature, but are in fact similar when adjusted for in vivo muscle temperatures, most likely to maintain intracellular O2 delivery in species adapted to different environments. It is unknown whether similar adaptations exist in the O2 affinity of Mb from reptiles, despite this group of ectothermic vertebrates displaying great variation in the tolerance to both temperature and hypoxia. In this study, we have purified Mb from muscle tissues of three reptilian species (turtle, tortoise and alligator) with different lifestyles. We have measured O2 binding characteristics and autoxidation rates of the three Mbs and measured the effects of temperature, lactate and blocking of reactive thiols on the O2 affinity of turtle Mb. Our data show that, at a constant temperature, reptilian Mbs have similar O2 affinities that are lower than those of mammalian Mbs, which may optimize intracellular O2 transport at lower body temperatures. Reptilian Mbs have lower autoxidation rates than both mammalian and fish Mbs, which may be beneficial during oxidative stress. Furthermore, the O2 affinity of turtle Mb is without allosteric control and independent of either lactate or thiol covalent modification. This study reveals some common adaptive patterns in the temperature-dependent regulation of Mb oxygenation in vertebrates. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Do low oxygen environments facilitate marine invasions? Relative tolerance of native and invasive species to low oxygen conditions.

    PubMed

    Lagos, Marcelo E; Barneche, Diego R; White, Craig R; Marshall, Dustin J

    2017-02-17

    Biological invasions are one of the biggest threats to global biodiversity. Marine artificial structures are proliferating worldwide and provide a haven for marine invasive species. Such structures disrupt local hydrodynamics, which can lead to the formation of oxygen-depleted microsites. The extent to which native fauna can cope with such low oxygen conditions, and whether invasive species, long associated with artificial structures in flow-restricted habitats, have adapted to these conditions remains unclear. We measured water flow and oxygen availability in marinas and piers at the scales relevant to sessile marine invertebrates (mm). We then measured the capacity of invasive and native marine invertebrates to maintain metabolic rates under decreasing levels of oxygen using standard laboratory assays. We found that marinas reduce water flow relative to piers, and that local oxygen levels can be zero in low flow conditions. We also found that for species with erect growth forms, invasive species can tolerate much lower levels of oxygen relative to native species. Integrating the field and laboratory data showed that up to 30% of available microhabitats within low flow environments are physiologically stressful for native species, while only 18% of the same habitat is physiologically stressful for invasive species. These results suggest that invasive species have adapted to low oxygen habitats associated with manmade habitats, and artificial structures may be creating niche opportunities for invasive species.

  18. Generation of reactive oxygen species by raphidophycean phytoplankton.

    PubMed

    Oda, T; Nakamura, A; Shikayama, M; Kawano, I; Ishimatsu, A; Muramatsu, T

    1997-10-01

    Chattonella marina, a raphidophycean flagellate, is one of the most toxic red tide phytoplankton and causes severe damage to fish farming. Recent studies demonstrated that Chattonella sp. generates superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radicals (.OH), which may be responsible for the toxicity of C. marina. In this study, we found the other raphidophycean flagellates such as Heterosigma akashiwo, Olisthodiscus luteus, and Fibrocapsa japonica also produce O2- and H2O2 under normal growth condition. Among the flagellate species tested, Chattonella has the highest rates of production of O2- and H2O2 as compared on the basis of cell number. This seems to be partly due to differences in their cell sizes, since Chattonella is larger than other flagellate species. The generation of O2- by these flagellate species was also confirmed by a chemiluminescence assay by using 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA). All these raphidophycean flagellates inhibited the proliferation of a marine bacterium, Vibrio alginolyticus, in a flagellates/bacteria co-culture system, and their toxic effects were suppressed by the addition of superoxide dismutase (SOD) or catalase. Our results suggest that the generation of reactive oxygen species is a common feature of raphidophycean flagellates.

  19. Laboratory investigations involving high-velocity oxygen atoms

    NASA Technical Reports Server (NTRS)

    Leger, Lubert J.; Koontz, Steven L.; Visentine, James T.; Cross, Jon B.

    1989-01-01

    Facilities for measuring material reactive characteristics have been under development for several years and span the atom energy range from thermal to 5 eV, the orbital collision energy. One of the high-atom energy facilities (The High Intensity/Energy Atomic Oxygen Source) capable of simulating the reactive part of LEO is described, along with results of beam characterization and preliminary material studies. The oxygen atom beam source was a continuous wave plasma produced by focusing a high-power CO2 laser through a lens system into a rare gas/molecular oxygen mixture chamber at elevated temperature. Material samples were exposed to the high velocity beam through an external feedthrough. The facility showed good stability in continued operation for more than 100 hours, producing fluences of 10 to the 21st to 10 to the 22nd atoms/sq cm. Reaction efficiencies and surface morphology have been measured for several materials at energies of 1.5 and 2.8 eV, matching with data generated from previous space flights. Activation energies for carbon and Kapton as measured in this facility were 800 cal/mole.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Kelm, Malte; Rassaf, Tienush

    2014-01-01

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

  2. Emissions of volatile organic compounds (primarily oxygenated species) from pasture

    NASA Astrophysics Data System (ADS)

    Kirstine, Wayne; Galbally, Ian; Ye, Yuerong; Hooper, Martin

    1998-05-01

    The volatile organic compound (VOC) emissions from pasture at a site in southeastern Victoria, Australia, were monitored over a 2 year period using a static chamber technique. Fluxes up to 23,000 μg(C) m-2 h-1 were detected, with the higher fluxes originating from clover rather than from grass species. Gas Chromatographic analyses indicated that emissions from both grass and clover were high in oxygenated hydrocarbons including methanol, ethanol, propanone, butanone, and ethanal, and extremely low in isoprene and monoterpenes. In the case of clover, butanone made up 45-50% of the total emissions. When grass and clover were freshly mown, there were significantly enhanced emissions of VOCs. These enhanced emissions included both those oxygenates emitted from uncut pasture and also C6-oxygenates, including (Z)-3-hexenal, (E)-2-hexenal, (Z)-2-hexen-1-ol, (Z)-3-hexen-l-ol, and (Z)-3-hexenyl acetate. Emissions from the undisturbed pasture increased markedly with temperature and the intensity of solar radiation, peaking at midday and ceasing at night. The fluxes, when normalized to a temperature of 30°C and a light intensity of 1000 μE m-2 s-1 were, for grass and clover respectively, about one eighth and two fifths of the equivalent fluxes reported to occur from U.S. woodlands. The annual integrated emission from the pasture was approximately 1.9 g(C) m-2 or 1.3 mg(C) g-1 (dry matter). The large transient fluxes that occurred following physical damaging of the pasture, when integrated over time, could be of the same order as those emissions that were observed from undisturbed pasture. In the case of methanol, and perhaps ethanol, the emissions from grasslands may be significant global sources of these gases.

  3. Reactive oxygen species: A radical role in development?

    PubMed

    Hernández-García, David; Wood, Christopher D; Castro-Obregón, Susana; Covarrubias, Luis

    2010-07-15

    Reactive oxygen species (ROS), mostly derived from mitochondrial activity, can damage various macromolecules and consequently cause cell death. This ROS activity has been characterized in vitro, and correlative evidence suggests a role in various pathological conditions. In addition to this passive ROS activity, ROS also participate in cell signaling processes, though the relevance of this function in vivo is poorly understood. Throughout development, elevated cell activity is probably accompanied by highly active metabolism and, consequently, the production of large amounts of ROS. To allow proper development, cells must protect themselves from these potentially damaging ROS. However, to what degree ROS could participate as signaling molecules controlling fundamental and developmentally relevant cellular processes such as proliferation, differentiation, and death is an open question. Here we discuss why available data do not yet provide conclusive evidence on the role of ROS in development, and we review recent methods to detect ROS in vivo and genetic strategies that can be exploited specifically to resolve these uncertainties.

  4. Role of Reactive Oxygen Species in Antibiotic Action and Resistance

    PubMed Central

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

    2009-01-01

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

  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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Reactive oxygen species in eradicating acute myeloid leukemic stem cells

    PubMed Central

    Zhang, Hui; Fang, Hai

    2014-01-01

    Leukemic stem cells (LSCs) have been proven to drive leukemia initiation, progression and relapse, and are increasingly being used as a critical target for therapeutic intervention. As an essential feature in LSCs, reactive oxygen species (ROS) homeostasis has been extensively exploited in the past decade for targeting LSCs in acute myeloid leukemia (AML). Most, if not all, agents that show therapeutic benefits are able to alter redox status by inducing ROS, which confers selectivity in eradicating AML stem cells but sparing normal counterparts. In this review, we provide the comprehensive update of ROS-generating agents in the context of their impacts on our understanding of the pathogenesis of AML and its therapy. We anticipate that further characterizing these ROS agents will help us combat against AML in the coming era of LSC-targeting strategy. PMID:27358859

  7. 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

  8. In vitro degradation of tropoelastin by reactive oxygen species.

    PubMed

    Hayashi, A; Ryu, A; Suzuki, T; Kawada, A; Tajima, S

    1998-09-01

    The effects of reactive oxygen species (ROS) on elastin molecules (tropoelastin) were studied in vitro. ROS generated by ultraviolet A and hematoporphyrin rapidly degraded tropoelastin within 5 min. Their degradative activity was inhibited by the addition of NaN3. Treatment of tropoelastin with copper sulfate/ascorbic acid resulted in degradation of tropoelastin producing fragments of molecular weight 45, 30 and 10 kDa within 30 min. The degradation of tropoelastin was partially blocked by the addition of mannitol. ROS induced by the xanthine/xanthine oxidase system also degraded tropoelastin within 6 h. The degradation was blocked by catalase but not by superoxide dismutase (SOD). ROS generated by copper-ascorbate seems to be unique in that it cleaves relatively specific sites of the tropoelastin molecule. Thus ROS may play a degradative role in elastin metabolism which may cause the elastolytic changes or the deposition of fragmented elastic fibers in photoaged skin or age-related elastolytic disorders.

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

    PubMed

    Premkumar, Louis S; Pabbidi, Reddy M

    2013-11-01

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

  10. Reactive oxygen species-activated nanomaterials as theranostic agents

    PubMed Central

    Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  11. Investigating the role of reactive oxygen species in regulating autophagy.

    PubMed

    Gibson, Spencer B

    2013-01-01

    Autophagy is an intracellular lysosomal degradation process induced under stress conditions. Reactive oxygen species (ROS) regulate autophagy implicated in cell survival, death, development, and many human diseases. This could be through generation of ROS from intracellular compartments such as the mitochondria or an external source such as oxidative stress. Various methods have been developed for the detection of autophagy; however, the implementation of these methods and the interpretation of results often differ. In this chapter, we summarize the current understanding of autophagy and ROS regulation of autophagy. Methods available for detecting autophagy under ROS conditions are described and considerations that need to be addressed when designing experimental protocols discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Reactive Oxygen Species in the Regulation of Stomatal Movements.

    PubMed

    Sierla, Maija; Waszczak, Cezary; Vahisalu, Triin; Kangasjärvi, Jaakko

    2016-07-01

    Guard cells form stomatal pores that optimize photosynthetic carbon dioxide uptake with minimal water loss. Stomatal movements are controlled by complex signaling networks that respond to environmental and endogenous signals. Regulation of stomatal aperture requires coordinated activity of reactive oxygen species (ROS)-generating enzymes, signaling proteins, and downstream executors such as ion pumps, transporters, and plasma membrane channels that control guard cell turgor pressure. Accumulation of ROS in the apoplast and chloroplasts is among the earliest hallmarks of stomatal closure. Subsequent increase in cytoplasmic Ca(2+) concentration governs the activity of multiple kinases that regulate the activity of ROS-producing enzymes and ion channels. In parallel, ROS directly regulate the activity of multiple proteins via oxidative posttranslational modifications to fine-tune guard cell signaling. In this review, we summarize recent advances in the role of ROS in stomatal closure and discuss the importance of ROS in regulation of signal amplification and specificity in guard cells.

  13. Bacterial persistence induced by salicylate via reactive oxygen species

    PubMed Central

    Wang, Tiebin; El Meouche, Imane; Dunlop, Mary J.

    2017-01-01

    Persisters are phenotypic variants of regular cells that exist in a dormant state with low metabolic activity, allowing them to exhibit high tolerance to antibiotics. Despite increasing recognition of their role in chronic and recalcitrant infections, the mechanisms that induce persister formation are not fully understood. In this study, we find that salicylate can induce persister formation in Escherichia coli via generation of reactive oxygen species (ROS). Salicylate-induced ROS cause a decrease in the membrane potential, reduce metabolism and lead to an increase in persistence. These effects can be recovered by culturing cells in the presence of a ROS quencher or in an anaerobic environment. Our findings reveal that salicylate-induced oxidative stress can lead to persistence, suggesting that ROS, and their subsequent impact on membrane potential and metabolism, may play a broad role in persister formation. PMID:28281556

  14. How reactive oxygen species and proline face stress together.

    PubMed

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

    2014-07-01

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

  15. 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.

  16. [The role of reactive oxygen species and mitochondria in aging].

    PubMed

    Piotrowska, Agnieszka; Bartnik, Ewa

    2014-01-01

    Aging is a biological phenomenon concerning all living multicellular organisms. Many studies have been conducted to identify the mechanisms underlying this process. To date, multiple theories have been proposed to explain the causes of aging. One of them is the free radical theory which postulates that reactive oxygen species (ROS), extremely reactive chemical molecules, are the major cause of the aging process. These free radicals are mainly produced by the mitochondrial respiratory chain as a result of electron transport and the reduction of the oxygen molecule. Toxic effects of ROS on cellular components lead to accumulation of oxidative damage which causes cellular dysfunction with age. The free radical theory has been one of the most popular theories of aging for many years. Scientific research on different model organisms aiming to verify the theory has produced abundant data, supporting the theory or, on the contrary, suggesting strong evidence against it. At present, the free radical theory of aging is no longer considered to be true.

  17. The immunopathogenic role of reactive oxygen species in Alzheimer disease.

    PubMed

    Mohsenzadegan, Monireh; Mirshafiey, Abbas

    2012-09-01

    Reactive oxygen species (ROS) are produced in many normal and abnormal processes in humans, including atheroma, asthma, joint diseases, cancer, and aging. Basal levels of ROS production in cells could be related to several physiological functions including cell proliferation, apoptosis and homeostasis. However, excessive ROS production above basal levels would impair and oxidize DNA, lipids, sugars and proteins and consequently result in dysfunction of these molecules within cells and finally cell death. A leading theory of the cause of aging indicates that free radical damage and oxidative stress play a major role in the pathogenesis of Alzheimer disease (AD). Because the brain utilizes 20% more oxygen than other tissues that also undergo mitochondrial respiration, the potential for ROS exposure increases. In fact, AD has been demonstrated to be highly associated with cellular oxidative stress, including augmentation of protein oxidation, protein nitration, glycoloxidation and lipid peroxidation as well as accumulation of Amyloid β (Aβ). The treatment with anti-oxidant compounds can provide protection against oxidative stress and Aβ toxicity. In this review, our aim was to clarify the role of ROS in pathogenesis of AD and will discuss therapeutic efficacy of some antioxidants studies in recent years in this disease.

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

    PubMed Central

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

    2008-01-01

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

  19. Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death.

    PubMed

    Ba, Ming-Chen; Long, Hui; Cui, Shu-Zhong; Gong, Yuan-Feng; Yan, Zhao-Fei; Wang, Shuai; Wu, Yin-Bing

    2017-06-01

    Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group. Reactive oxygen species production and expression of autophagy-related genes Beclin1, LC3B, and mammalian target of rapamycin were determined. The relationships between tumor growth regression, expression of autophagy-related genes, and reactive oxygen species production were evaluated. Tumor size and wet weight of hyperthermia + chemotherapy group was significantly decreased relative to values from hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group ( F = 6.92, p < 0.01 and F = 5.36, p < 0.01, respectively). Reactive oxygen species production was significantly higher in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. The expression levels of Beclin1 and LC3B were significantly higher, while those of mammalian target of rapamycin were significantly lower in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. Tumor growth regression was consistent with changes in reactive oxygen species production and expression of autophagy-related genes. N-acetyl-L-cysteine inhibited changes in the expression of the autophagy-related genes and also suppressed reactive oxygen species production and tumor growth. Hyperthermia + chemotherapy increase expression of autophagy-related genes Beclin1 and LC3B, decrease expression of mammalian target of rapamycin, and concomitantly increase reactive oxygen species generation. These results strongly indicate

  20. 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.

  1. 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.

  2. Nanotechnology for Electroanalytical Biosensors of Reactive Oxygen and Nitrogen Species.

    PubMed

    Seenivasan, Rajesh; Kolodziej, Charles; Karunakaran, Chandran; Burda, Clemens

    2017-09-01

    Over the past several decades, nanotechnology has contributed to the progress of biomedicine, biomarker discovery, and the development of highly sensitive electroanalytical / electrochemical biosensors for in vitro and in vivo monitoring, and quantification of oxidative and nitrosative stress markers like reactive oxygen species (ROS) and reactive nitrogen species (RNS). A major source of ROS and RNS is oxidative stress in cells, which can cause many human diseases, including cancer. Therefore, the detection of local concentrations of ROS (e. g. superoxide anion radical; O2(•-) ) and RNS (e. g. nitric oxide radical; NO(•) and its metabolites) released from biological systems is increasingly important and needs a sophisticated detection strategy to monitor ROS and RNS in vitro and in vivo. In this review, we discuss the nanomaterials-based ROS and RNS biosensors utilizing electrochemical techniques with emphasis on their biomedical applications. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

    McCormick, Rachel; Pearson, Timothy; Vasilaki, Aphrodite

    2016-08-01

    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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    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

  6. Inflammatory joint disease: the role of cytokines, cyclooxygenases and reactive oxygen species.

    PubMed

    Moulton, P J

    1996-12-01

    Cytokines are known to have a key role in the onset and development of inflammatory joint disease, including rheumatoid arthritis and osteoarthritis. The effects of some cytokines on the cells and tissues involved in inflammation of the joint are well catalogued, but recent discoveries of new cytokines, and interest in intracellular signalling molecules, have thrown new light on the way in which cytokines mediate the cellular responses that lead to inflammation. Here, recent work on the roles of cytokines, cyclooxygenases, nitric oxide and other reactive oxygen species, in the cellular pathways that lead from cytokine receptor to inflammation, are discussed.

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

    PubMed Central

    Adam-Vizi, Vera; Starkov, Anatoly A.

    2011-01-01

    A number of recent discoveries indicate that abnormal Ca2+ signaling, oxidative stress, and mitochondrial dysfunction are involved in the neuronal damage in Alzheimer’s disease. However, the literature on the interactions between these factors is controversial especially in the interpretation of the cause-effect relationship between mitochondrial damage induced by Ca2+ overload and the production of reactive oxygen species (ROS). In this review, we survey the experimental observations on the Ca2+-induced mitochondrial ROS production, explain the sources of controversy in interpreting these results, and discuss the different molecular mechanisms underlying the effect of Ca2+ on the ROS emission by brain mitochondria. PMID:20421693

  8. Calcium and mitochondrial reactive oxygen species generation: how to read the facts.

    PubMed

    Adam-Vizi, Vera; Starkov, Anatoly A

    2010-01-01

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

  9. Signaling of Reactive Oxygen and Nitrogen Species in Diabetes Mellitus

    PubMed Central

    Afanas'ev, Igor

    2010-01-01

    Disorder of physiological signaling functions of reactive oxygen species(ROS) superoxide and hydrogen peroxide and reactive nitrogen species (RNS) nitric oxide and peroxynitrite is an important feature of diabetes mellitus type 1 and type 2. It is now known that hyperglycemic conditions of cells are associated with the enhanced levels of ROS mainly generated by mitochondria and NADPH oxidase. It has been established that ROS stimulate many enzymatic cascades under normal physiological conditions, but hyperglycemia causes ROS overproduction and the deregulation of ROS signaling pathways initiating the development of diabetes mellitus. On the other hand the deregulation of RNS signaling leads basically to a decrease in NO formation with subsequent damaging disorders. In the present work we will consider the pathological changes of ROS and RNS signaling in enzyme/gene regulated processes catalyzed by protein kinases C and B (Akt/B), phosphatidylinositol 3′-kinase (PI3-kinase), extracellular signal-regulated kinase 1/2 (ERK1/2) and some others. Furthermore we will discuss a particularly important role of several ROS-regulated genes and adapter proteins such as the p66shc, FOXO3a and Sirt2. The effects of low and high ROS levels in diabetes will be also considered. Thus the regulation of damaging ROS levels in diabetes by antioxidants and free radical scavengers must be one of promising treatment of this disease, however, because of the inability of traditionalantioxidative vitamin E and C to interact with superoxide and hydrogen peroxide,new free radical scavengers such as flavonoids, quinones and synthetic mimetics of superoxide dismutase (SOD) should be intensively studied. PMID:21311214

  10. Plasma-generated reactive oxygen species for biomedical applications

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  11. Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: implications for hypoxic cell signaling.

    PubMed

    Hoffman, David L; Salter, Jason D; Brookes, Paul S

    2007-01-01

    Mitochondria are proposed to play an important role in hypoxic cell signaling. One currently accepted signaling paradigm is that the mitochondrial generation of reactive oxygen species (ROS) increases in hypoxia. This is paradoxical, because oxygen is a substrate for ROS generation. Although the response of isolated mitochondrial ROS generation to [O(2)] has been examined previously, such investigations did not apply rigorous control over [O(2)] within the hypoxic signaling range. With the use of open-flow respirometry and fluorimetry, the current study determined the response of isolated rat liver mitochondrial ROS generation to defined steady-state [O(2)] as low as 0.1 microM. In mitochondria respiring under state 4 (quiescent) or state 3 (ATP turnover) conditions, decreased ROS generation was always observed at low [O(2)]. It is concluded that the biochemical mechanism to facilitate increased ROS generation in response to hypoxia in cells is not intrinsic to the mitochondrial respiratory chain alone but may involve other factors. The implications for hypoxic cell signaling are discussed.

  12. Reactive oxygen species at the crossroads of inflammasome and inflammation

    PubMed Central

    Harijith, Anantha; Ebenezer, David L.; Natarajan, Viswanathan

    2014-01-01

    Inflammasomes form a crucial part of the innate immune system. These are multi-protein oligomer platforms that are composed of intracellular sensors which are coupled with caspase and interleukin activating systems. Nod-like receptor protein (NLRP) 3, and 6 and NLRC4 and AIM2 are the prominent members of the inflammasome family. Inflammasome activation leads to pyroptosis, a process of programmed cell death distinct from apoptosis through activation of Caspase and further downstream targets such as IL-1β and IL-18 leading to activation of inflammatory cascade. Reactive oxygen species (ROS) serves as important inflammasome activating signals. ROS activates inflammasome through mitogen-activated protein kinases (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Dysregulation of inflammasome plays a significant role in various pathological processes. Viral infections such as Dengue and Respiratory syncytial virus activate inflammasomes. Crystal compounds in silicosis and gout also activate ROS. In diabetes, inhibition of autophagy with resultant accumulation of dysfunctional mitochondria leads to enhanced ROS production activating inflammasomes. Activation of inflammasomes can be dampened by antioxidants such as SIRT-1. Inflammasome and related cascade could serve as future therapeutic targets for various pathological conditions. PMID:25324778

  13. Reactive Oxygen Species Regulate Protrusion Efficiency by Controlling Actin Dynamics

    PubMed Central

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

    2012-01-01

    Productive protrusions allowing motile cells to sense and migrate toward a chemotactic gradient of reactive oxygen species (ROS) require a tight control of the actin cytoskeleton. However, the mechanisms of how ROS affect cell protrusion and actin dynamics are not well elucidated yet. We show here that ROS induce the formation of a persistent protrusion. In migrating epithelial cells, protrusion of the leading edge requires the precise regulation of the lamellipodium and lamella F-actin networks. Using fluorescent speckle microscopy, we showed that, upon ROS stimulation, the F-actin retrograde flow is enhanced in the lamellipodium. This event coincides with an increase of cofilin activity, free barbed ends formation, Arp2/3 recruitment, and ERK activity at the cell edge. In addition, we observed an acceleration of the F-actin flow in the lamella of ROS-stimulated cells, which correlates with an enhancement of the cell contractility. Thus, this study demonstrates that ROS modulate both the lamellipodium and the lamella networks to control protrusion efficiency. PMID:22876286

  14. 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

  15. 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

  16. Generation of reactive oxygen species from silicon nanowires.

    PubMed

    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.

  17. Production of ozone and reactive oxygen species after welding.

    PubMed

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

    2007-11-01

    Many toxic substances including heavy metals, ozone, carbon monoxide, carbon dioxide, and nitrogen oxides are generated during welding. Ozone (O(3)) is a strong oxidant that generates reactive oxygen species (ROS) in tissue, and ambient ROS exposure associated with particles has been determined to cause DNA damage. Ozone is produced within 30 seconds during welding. However, the length of time that O(3) remains in the air after welding is completed (post-welding) is unknown. The current study aimed to assess the distributions of ambient ROS and O(3) before the start of welding (pre-welding), during welding, and after welding. The highest O(3) levels, equal to 195 parts per billion (ppb), appeared during welding. Ozone levels gradually decreased to 60 ppb 10 minutes after the welding was completed. The highest ROS level was found in samples taken during welding, followed by samples taken after the welding was completed. The lowest ROS level was found in samples taken before the welding had started. Ozone and ROS levels were poorly correlated, but a similar trend was found for O(3) and ROS levels in particles (microM/mg). Although particles were not generated after welding, ROS and O(3) still persisted for more than 10 minutes. Meanwhile, because O(3) continues after welding, how long the occupational protective system should be used depends on the welding materials and the methods used. In addition, the relationship between metal fumes and ROS generation during the welding process should be further investigated.

  18. Reactive oxygen species at the crossroads of inflammasome and inflammation.

    PubMed

    Harijith, Anantha; Ebenezer, David L; Natarajan, Viswanathan

    2014-01-01

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

  19. Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species.

    PubMed

    Bao, Hui-Fang; Song, John Z; Duke, Billie J; Ma, He-Ping; Denson, Donald D; Eaton, Douglas C

    2012-12-01

    Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (P(o)) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC P(o) and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde.

  20. Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species.

    PubMed

    Starkov, Anatoly A; Fiskum, Gary; Chinopoulos, Christos; Lorenzo, Beverly J; Browne, Susan E; Patel, Mulchand S; Beal, M Flint

    2004-09-08

    Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H(2)O(2) production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p-trifluoromethoxyphenylhydrazone,alpha-ketoglutarate supported the highest rate of H(2)O(2) production. In the absence of ADP or in the presence of rotenone, H(2)O(2) production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of alpha-ketoglutarate. Isolated mitochondrial alpha-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H(2)O(2). NAD(+) inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H(2)O(2) production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H(2)O(2) than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria.

  1. 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

  2. Imaging Reactive Oxygen Species-Induced Modifications in Living Systems

    PubMed Central

    Maulucci, Giuseppe; Bačić, Goran; Bridal, Lori; Schmidt, Harald H.H.W.; Tavitian, Bertrand; Viel, Thomas; Utsumi, Hideo; Yalçın, A. Süha

    2016-01-01

    Abstract Significance: Reactive Oxygen Species (ROS) may regulate signaling, ion channels, transcription factors, and biosynthetic processes. ROS-related diseases can be due to either a shortage or an excess of ROS. Recent Advances: Since the biological activity of ROS depends on not only concentration but also spatiotemporal distribution, real-time imaging of ROS, possibly in vivo, has become a need for scientists, with potential for clinical translation. New imaging techniques as well as new contrast agents in clinically established modalities were developed in the previous decade. Critical Issues: An ideal imaging technique should determine ROS changes with high spatio-temporal resolution, detect physiologically relevant variations in ROS concentration, and provide specificity toward different redox couples. Furthermore, for in vivo applications, bioavailability of sensors, tissue penetration, and a high signal-to-noise ratio are additional requirements to be satisfied. Future Directions: None of the presented techniques fulfill all requirements for clinical translation. The obvious way forward is to incorporate anatomical and functional imaging into a common hybrid-imaging platform. Antioxid. Redox Signal. 24, 939–958. PMID:27139586

  3. Reactive Oxygen Species (ROS): Beneficial Companions of Plants’ Developmental Processes

    PubMed Central

    Singh, Rachana; Singh, Samiksha; Parihar, Parul; Mishra, Rohit K.; Tripathi, Durgesh K.; Singh, Vijay P.; Chauhan, Devendra K.; Prasad, Sheo M.

    2016-01-01

    Reactive oxygen species (ROS) are generated inevitably in the redox reactions of plants, including respiration and photosynthesis. In earlier studies, ROS were considered as toxic by-products of aerobic pathways of the metabolism. But in recent years, concept about ROS has changed because they also participate in developmental processes of plants by acting as signaling molecules. In plants, ROS regulate many developmental processes such as cell proliferation and differentiation, programmed cell death, seed germination, gravitropism, root hair growth and pollen tube development, senescence, etc. Despite much progress, a comprehensive update of advances in the understanding of the mechanisms evoked by ROS that mediate in cell proliferation and development are fragmentry and the matter of ROS perception and the signaling cascade remains open. Therefore, keeping in view the above facts, an attempt has been made in this article to summarize the recent findings regarding updates made in the regulatory action of ROS at various plant developmental stages, which are still not well-known. PMID:27729914

  4. Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species

    PubMed Central

    Bao, Hui-Fang; Song, John Z.; Duke, Billie J.; Ma, He-Ping; Denson, Donald D.

    2012-01-01

    Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (Po) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC Po and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde. PMID:22895258

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

    PubMed

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

    2017-02-28

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

  6. Reactive oxygen species in response of plants to gravity stress

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy

    2016-07-01

    Reactive oxygen species (ROS) as second messengers can induce stress response of plants. Thioredoxins (Trx) and peroxiredoxins (Prx) can function as sensors and transmitters of the ROS in stress signaling and antioxidant response. 12-14 days old tissue culture of Arabidopsis thaliana have been investigated. Hypergravity stress was induced by centrifugation at 10 and 20 g during 30 and 90 min and than intensity of spontaneous chemiluminescence (SChL/ROS content), Trx and Prx activities were determined. All experiments were repeated from 3 to 5 times and the obtained data were statistically treated. In the tissue culture under development of the stress there were an increase in intensity of SChL and Trx and Prx activities. Thus, under hypergravity stress in the plant occurred early increase in the ROS level and the ROS induced the increase in the Trx and Prx activities. Prx and Trx can also participate in the formation of stress respons as acceptors and transducers of the redox signals. Increase in the activity of these enzymes primarily aimed at increasing of the total antioxidant activity in the cells to prevent of the plant to development of oxidative degradation by ROS.

  7. Geochemical production of reactive oxygen species from biogeochemically reduced Fe.

    PubMed

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

    2014-04-01

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

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

    PubMed

    Benedetti, Serena; Nuvoli, Barbara; Catalani, Simona; Galati, Rossella

    2015-07-10

    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.

  9. 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

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

    PubMed

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

    2015-12-01

    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.

  11. Soot-driven reactive oxygen species formation from incense burning.

    PubMed

    Chuang, Hsiao-Chi; Jones, Tim P; Lung, Shih-Chun C; BéruBé, Kelly A

    2011-10-15

    This study investigated the effects of reactive oxygen species (ROS) generated as a function of the physicochemistry of incense particulate matter (IPM), diesel exhaust particles (DEP) and carbon black (CB). Microscopical and elemental analyses were used to determine particle morphology and inorganic compounds. ROS was determined using the reactive dye, Dichlorodihydrofluorescin (DCFH), and the Plasmid Scission Assay (PSA), which determine DNA damage. Two common types of soot were observed within IPM, including nano-soot and micro-soot, whereas DEP and CB mainly consisted of nano-soot. These PM were capable of causing oxidative stress in a dose-dependent manner, especially IPM and DEP. A dose of IPM (36.6-102.3μg/ml) was capable of causing 50% oxidative DNA damage. ROS formation was positively correlated to smaller nano-soot aggregates and bulk metallic compounds, particularly Cu. These observations have important implications for respiratory health given that inflammation has been recognised as an important factor in the development of lung injury/diseases by oxidative stress. This study supports the view that ROS formation by combustion-derived PM is related to PM physicochemistry, and also provides new data for IPM.

  12. 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

  13. Signaling by reactive oxygen and nitrogen species in skin diseases.

    PubMed

    Afanas'ev, Igor B

    2010-06-01

    For many years the formation of reactive oxygen and nitrogen species (ROS) and (RNS) in living organisms has been considered to be dangerous phenomenon due to their damaging action on biomolecules. However, present studies demonstrated another important activity of ROS and RNS: their signaling functions in physiological and pathological processes. In this work we discuss the new data concerning a role of ROS and RNS in many enzymatic/gene cascades causing damaging changes during the development of skin diseases and pathological disorders (skin cancer, the toxic effects of irradiation on the skin, and skin wounding). It has been suggested that the enhancement of ROS formation in tumor cells through the inactivation of mitochondrial MnSOD or the activation of NADPH oxidase leads to apoptosis and might be applied for developing a new cancer therapy. On the other hand ROS overproduction might stimulate malignant transformation of melanoma. Role of ROS signaling is also considered in the damaging action of UVA, UVB, and IRA irradiation on the skin and the processes of wound healing. In the last part of review the possibility of the right choice of antioxidants and free radical scavengers for the treatment of skin disease is discussed.

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

    PubMed

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

    2017-09-01

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

  15. 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

  16. Vascular-derived reactive oxygen species for homeostasis and diseases.

    PubMed

    Satoh, Kimio; Berk, Bradford C; Shimokawa, Hiroaki

    2011-08-01

    Numerous basic and clinical studies have clearly identified that reactive oxygen species (ROS, i.e., H(2)O(2), O(2)(-), and ()OH) has a major role in the development of cardiovascular diseases. However, we still have no strong therapeutic strategy for clinical benefits of antioxidant administration. One potential reason for those could be a crucial role of ROS for intracellular signaling pathways that is important for vascular functions in a very low concentration. ROS contributes to the physiology and pathology of vasculature, but precise molecular regulations remain elusive. The mechanism how excessive ROS (oxidative stress) deteriorate vascular function and promote vascular diseases has not been clearly elucidated. Cyclophilin A (CyPA) has been studied as a multifunctional protein that is upregulated in a variety of inflammatory conditions, such as rheumatoid arthritis, autoimmune disease, and cancer. CyPA has been classified as an immunophilins and has a variety of intracellular functions including intracellular signaling, protein trafficking, and the regulating other proteins. Besides intracellular functions, we revealed that CyPA is a secreted molecule that has a pathological role in the cardiovascular system. CyPA has emerged as a potential biomarker and mediator of cardiovascular disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 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

  18. Serum levels of reactive oxygen species (ROS) in the bitch.

    PubMed

    Rizzo, Annalisa; Roscino, Maria Teresa; Minoia, Giuseppe; Trisolini, Carmelinda; Spedicato, Massimo; Mutinati, Maddalena; Pantaleo, Marianna; Jirillo, Felicita; Sciorsci, Raffaele L

    2009-06-01

    The aim of this study was to determine the serum concentrations of reactive oxygen species (ROS) during the different phases of the estrous cycle in the bitch, in order to establish their physiological values. 56 healthy mixed-breed bitches were enrolled at this purpose and divided into 4 groups, standing on the different phases of the estrus cycle. Blood samples were collected in all groups and serum ROS concentrations were determined. Proestral concentrations were statistically higher than anestral ones, and statistically lower than those found in estrus (p<0.001). The highest concentrations of ROS were detected at estrus, that is, in the peri-ovulatory period. This sharp increase in ROS concentrations is related to the acute inflammatory process underlying ovulation and to the increase in immune and metabolic activities, cytological changes and myometrial contractility promoted by the high levels of estrogens. In diestrus, the mean concentration of ROS decreases. This reduction did not show any statistically significant difference with the mean value observed in proestrus. In this phase, in fact, the high concentrations of progesterone, exerting an antioxidant and immunodepressive effect, justify the lower mean concentration of ROS detected. In anestrus, the lowest concentrations of ROS were observed, for the reduced metabolic and endocrine activity occurring in this phase of the estrous cycle. In conclusion our results establish the physiologic levels of ROS during the estrous cycle in the bitch and reflect the endocrine morphologic and metabolic changes occurring during it.

  19. Carbocisteine can scavenge reactive oxygen species in vitro.

    PubMed

    Nogawa, Hisashi; Ishibashi, Yuji; Ogawa, Akitsu; Masuda, Kayoko; Tsubuki, Takeshi; Kameda, Tomoko; Matsuzawa, Shigeki

    2009-01-01

    Reactive oxygen species (ROS) play an important role in the pathogenesis of various respiratory diseases. Carbocisteine, a mucoregulatory drug, is used in the treatment of several disease states but little information is available about its scavenger effects on ROS. The present study was designed to examine the scavenger effects of carbocisteine on ROS. The oxidation-reduction potential of carbocisteine was measured, and its scavenger effects on hypochlorous acid (HOCl), hydrogen peroxide (H(2)O(2)), hydroxyl radical (OH(*)) and peroxynitrite (ONOO(-)) were examined in cell-free conditions. The effects of carbocisteine on ROS generated from rat neutrophils, intracellular oxidative stress and release of inflammatory cytokines (IL-8 and IL-6) from IL-1 beta-induced airway epithelial cells, NCI-H292 cells, were investigated. Carbocisteine provided a reducing stage and showed scavenger effects on H(2)O(2), HOCl, OH(*) and ONOO(-) in cell-free conditions. Carbocisteine inhibited ROS generation from rat neutrophils, intracellular oxidative stress and release of IL-8 and IL-6 from NCI-H292 cells. N-acetyl-L-cysteine, a radical scavenger, also inhibited these events related to ROS as well as carbocisteine. These results suggest that carbocisteine could exert anti-inflammatory and anti-oxidant effects through directly scavenging ROS in addition to its previously known mucoregulatory effect.

  20. 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

  1. Redox Mechanism of Reactive Oxygen Species in Exercise

    PubMed Central

    He, Feng; Li, Juan; Liu, Zewen; Chuang, Chia-Chen; Yang, Wenge; Zuo, Li

    2016-01-01

    It is well known that regular exercise can benefit health by enhancing antioxidant defenses in the body. However, unaccustomed and/or exhaustive exercise can generate excessive reactive oxygen species (ROS), leading to oxidative stress-related tissue damages and impaired muscle contractility. ROS are produced in both aerobic and anaerobic exercise. Mitochondria, NADPH oxidases and xanthine oxidases have all been identified as potential contributors to ROS production, yet the exact redox mechanisms underlying exercise-induced oxidative stress remain elusive. Interestingly, moderate exposure to ROS is necessary to induce body's adaptive responses such as the activation of antioxidant defense mechanisms. Dietary antioxidant manipulation can also reduce ROS levels and muscle fatigue, as well as enhance exercise recovery. To elucidate the complex role of ROS in exercise, this review updates on new findings of ROS origins within skeletal muscles associated with various types of exercises such as endurance, sprint and mountain climbing. In addition, we will examine the corresponding antioxidant defense systems as well as dietary manipulation against damages caused by ROS. PMID:27872595

  2. 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.

  3. On the in vivo photochemical rate parameters for PDT reactive oxygen species modeling

    NASA Astrophysics Data System (ADS)

    Kim, Michele M.; Ghogare, Ashwini A.; Greer, Alexander; Zhu, Timothy C.

    2017-03-01

    Photosensitizer photochemical parameters are crucial data in accurate dosimetry for photodynamic therapy (PDT) based on photochemical modeling. Progress has been made in the last few decades in determining the photochemical properties of commonly used photosensitizers (PS), but mostly in solution or in vitro. Recent developments allow for the estimation of some of these photochemical parameters in vivo. This review will cover the currently available in vivo photochemical properties of photosensitizers as well as the techniques for measuring those parameters. Furthermore, photochemical parameters that are independent of environmental factors or are universal for different photosensitizers will be examined. Most photosensitizers discussed in this review are of the type II (singlet oxygen) photooxidation category, although type I photosensitizers that involve other reactive oxygen species (ROS) will be discussed as well. The compilation of these parameters will be essential for ROS modeling of PDT.

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

    PubMed Central

    Waris, Gulam; Ahsan, Haseeb

    2006-01-01

    Oxygen derived species such as superoxide radical, hydrogen peroxide, singlet oxygen and hydroxyl radical are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. The changes in DNA such as base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication and the activation of oncogenes may be involved in the initiation of various cancers. Elevated levels of ROS and down regulation of ROS scavengers and antioxidant enzymes are associated with various human diseases including various cancers. ROS are also implicated in diabtes and neurodegenerative diseases. ROS influences central cellular processes such as proliferation a, apoptosis, senescence which are implicated in the development of cancer. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention. PMID:16689993

  5. UV-B-Induced PR-1 Accumulation Is Mediated by Active Oxygen Species.

    PubMed

    Green, R.; Fluhr, R.

    1995-02-01

    Depletion of the stratospheric ozone layer may result in an increase in the levels of potentially harmful UV-B radiation reaching the surface of the earth. We have found that UV-B is a potent inducer of the plant pathogenesis-related protein PR-1 in tobacco leaves. UV-B fluences required for PR-1 accumulation are similar to those of other UV-B-induced responses. The UV-B-induced PR-1 accumulation was confined precisely to the irradiated area of the leaf but displayed no leaf tissue specificity. A study of some of the possible components of the signal transduction pathway between UV-B and PR-1 induction showed that photosynthetic processes are not essential, and photoreversible DNA damage is not involved. Antioxidants and cycloheximide were able to block the induction of PR-1 by UV-B, and treatment of leaves with a generator of reactive oxygen resulted in the accumulation of PR-1 protein. These results demonstrate an absolute requirement for active oxygen species and protein synthesis in this UV-B signal transduction pathway. In contrast, we also show that other elicitors, notably salicylic acid, are able to elicit PR-1 via nonreactive oxygen species-requiring pathways.

  6. 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

  7. 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

    2016-02-02

    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.

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

    PubMed

    Criado, Susana; García, Norman A

    2010-01-01

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

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

    PubMed Central

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

    1992-01-01

    We have assessed the stoichiometry of the nitric oxide (NO) synthase reaction by using a novel e.p.r. technique. NO generated by crude and partially purified NO synthase from endothelial cells and Escherichia coli-lipopolysaccharide-activated macrophages was trapped by a ferrous diethyldithiocarbamate complex dispersed in yeast. The paramagnetic ferrous mononitrosyl dithiocarbamate complex formed exhibited a characteristic e.p.r. signal at g perpendicular = 2.035 and g parallel = 2.02 with a triplet hyperfine structure (hfs) at g perpendicular. NO, 3-morpholinosydnonimine and S-nitroso-L-cysteine, but not nitrite or hydroxylamine, generated a similar e.p.r. signal. NO generated by NO synthase and by SIN-1 accumulated at a constant rate for 1 h, as measured by continuous e.p.r. registration at 37 degrees C. The formation of e.p.r.-detectable NO by NO synthases was inhibited by NG-nitro-L-arginine. Incubation with [15N]NG-L-arginine caused an e.p.r. signal with doublet hfs, indicating that the nitrosyl nitrogen derived exclusively from the guanidino nitrogen. The amount of NO generated by NO synthase as measured by e.p.r. technique was compared with formation of L-[3H]citrulline from L-[3H]arginine. NO and L-citrulline were detected at a 1:1 ratio with both NO synthase preparations. GSH and thiol depletion did not significantly affect NO synthase activity, excluding S-nitrosothiols as intermediates in the NO synthase reaction. We conclude that NO fully accounts for the immediate oxygenated nitrogen species derived from the enzymic oxygenation of L-arginine. PMID:1281408

  10. Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System

    PubMed Central

    Griendling, Kathy K.; Touyz, Rhian M.; Zweier, Jay L.; Dikalov, Sergey; Chilian, William; Chen, Yeong-Renn; Harrison, David G.; Bhatnagar, Aruni

    2017-01-01

    Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accuracy and precision. In this statement, we review current methods for measuring these species and the secondary products they generate and suggest approaches for measuring redox status, oxidative stress, and the production of individual reactive oxygen and nitrogen species. We discuss the strengths and limitations of different methods and the relative specificity and suitability of these methods for measuring the concentrations of reactive oxygen and reactive nitrogen species in cells, tissues, and biological fluids. We provide specific guidelines, through expert opinion, for choosing reliable and reproducible assays for different experimental and clinical situations. These guidelines are intended to help investigators and clinical researchers avoid experimental error and ensure high-quality measurements of these important biological species. PMID:27418630

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

    PubMed Central

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

    2016-01-01

    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

  12. 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.

  13. 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

  14. 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.

  15. Reactive Oxygen Species Tune Root Tropic Responses1[OPEN

    PubMed Central

    Krieger, Gat

    2016-01-01

    The default growth pattern of primary roots of land plants is directed by gravity. However, roots possess the ability to sense and respond directionally to other chemical and physical stimuli, separately and in combination. Therefore, these root tropic responses must be antagonistic to gravitropism. The role of reactive oxygen species (ROS) in gravitropism of maize and Arabidopsis (Arabidopsis thaliana) roots has been previously described. However, which cellular signals underlie the integration of the different environmental stimuli, which lead to an appropriate root tropic response, is currently unknown. In gravity-responding roots, we observed, by applying the ROS-sensitive fluorescent dye dihydrorhodamine-123 and confocal microscopy, a transient asymmetric ROS distribution, higher at the concave side of the root. The asymmetry, detected at the distal elongation zone, was built in the first 2 h of the gravitropic response and dissipated after another 2 h. In contrast, hydrotropically responding roots show no transient asymmetric distribution of ROS. Decreasing ROS levels by applying the antioxidant ascorbate, or the ROS-generation inhibitor diphenylene iodonium attenuated gravitropism while enhancing hydrotropism. Arabidopsis mutants deficient in Ascorbate Peroxidase 1 showed attenuated hydrotropic root bending. Mutants of the root-expressed NADPH oxidase RBOH C, but not rbohD, showed enhanced hydrotropism and less ROS in their roots apices (tested in tissue extracts with Amplex Red). Finally, hydrostimulation prior to gravistimulation attenuated the gravistimulated asymmetric ROS and auxin signals that are required for gravity-directed curvature. We suggest that ROS, presumably H2O2, function in tuning root tropic responses by promoting gravitropism and negatively regulating hydrotropism. PMID:27535793

  16. 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.

  17. The impact of reactive oxygen species on anticancer therapeutic strategies.

    PubMed

    Ivanova, Donika; Bakalova, Rumiana; Lazarova, Dessisslava; Gadjeva, Veselina; Zhelev, Zhivko

    2013-01-01

    Over 50 years of experience in free radical biology and medicine shows that normal cells of healthy mammals are characterized by a low steady-state level of reactive oxygen species (ROS) and a constant (reference) level of reducing equivalents. A lasting increase of ROS above the critical level leads to permanent oxidative stress in the cells. This could cause genomic instability and mutations, which are responsible for adaptation of cells to oxidative stress and their survival in an oxidative environment. In turn, these events could provoke malignancy. It is widely accepted that the balance between ROS and reducing equivalents in cells and tissues determines their redox status. The evaluation of tissue redox status has great diagnostic potential in cancer, as well as prognostic potential for cancer therapy, and could significantly contribute to the planning of appropriate treatment and to increasing the patients' quality of life. The conventional therapeutic strategy is based on drugs that increase ROS generation and induce apoptosis in cancer cells. However, this therapeutic approach has serious disadvantages: the expression of various toxic side effects in normal (non-cancer) tissues. The current review describes the basics of free radical biology in carcinogenesis. The authors emphasize the different redox status of normal and cancer cells, which permits the use of this parameter as a new therapeutic target. The authors also outline some directions for the development of promising therapeutic strategies based on the regulation of redox signaling using combined therapy. The review is intended for a broad readership - from non-specialists to researchers in the field of cancer biochemistry and pharmacy.

  18. 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.

  19. Phylogeographic support for horizontal gene transfer involving sympatric bruchid species

    PubMed Central

    Alvarez, Nadir; Benrey, Betty; Hossaert-McKey, Martine; Grill, Andrea; McKey, Doyle; Galtier, Nicolas

    2006-01-01

    pseudogenisation. However, none of these seem able to explain the patterns observed. A fourth hypothesis, involving recent horizontal gene transfer (HGT) between A. obtectus and A. obvelatus, and from one of these species to Z. subfasciatus in the Mexican Altiplano, seems the only plausible explanation. The HGT between our study species seems to have occurred recently, and only in a zone where the three beetles are sympatric and share common host plants. This suggests that transfer could have been effected by some external vector such as a eukaryotic or viral parasite, which might still host the transferred fragment. Reviewers This article was reviewed by Eric Bapteste, Adam Eyre-Walker and Alexey Kondrashov. PMID:16872524

  20. Growth enhancement and gene expression of Arabidopsis thaliana irradiated with active oxygen species

    NASA Astrophysics Data System (ADS)

    Watanabe, Satoshi; Ono, Reoto; Hayashi, Nobuya; Shiratani, Masaharu; Tashiro, Kosuke; Kuhara, Satoru; Inoue, Asami; Yasuda, Kaori; Hagiwara, Hiroko

    2016-07-01

    The characteristics of plant growth enhancement effect and the mechanism of the enhancement induced by plasma irradiation are investigated using various active species in plasma. Active oxygen species in oxygen plasma are effective for growth enhancement of plants. DNA microarray analysis of Arabidopsis thaliana indicates that the genes coding proteins that counter oxidative stresses by eliminating active oxygen species are expressed at significantly high levels. The size of plant cells increases owing to oxygen plasma irradiation. The increases in gene expression levels and cell size suggest that the increase in the expression level of the expansin protein is essential for plant growth enhancement phenomena.

  1. Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions.

    PubMed

    Hoffman, David L; Brookes, Paul S

    2009-06-12

    The mitochondrial generation of reactive oxygen species (ROS) plays a central role in many cell signaling pathways, but debate still surrounds its regulation by factors, such as substrate availability, [O2] and metabolic state. Previously, we showed that in isolated mitochondria respiring on succinate, ROS generation was a hyperbolic function of [O2]. In the current study, we used a wide variety of substrates and inhibitors to probe the O2 sensitivity of mitochondrial ROS generation under different metabolic conditions. From such data, the apparent Km for O2 of putative ROS-generating sites within mitochondria was estimated as follows: 0.2, 0.9, 2.0, and 5.0 microM O2 for the complex I flavin site, complex I electron backflow, complex III QO site, and electron transfer flavoprotein quinone oxidoreductase of beta-oxidation, respectively. Differential effects of respiratory inhibitors on ROS generation were also observed at varying [O2]. Based on these data, we hypothesize that at physiological [O2], complex I is a significant source of ROS, whereas the electron transfer flavoprotein quinone oxidoreductase may only contribute to ROS generation at very high [O2]. Furthermore, we suggest that previous discrepancies in the assignment of effects of inhibitors on ROS may be due to differences in experimental [O2]. Finally, the data set (see supplemental material) may be useful in the mathematical modeling of mitochondrial metabolism.

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

    PubMed Central

    Cano, Isaac; Selivanov, Vitaly; Gomez-Cabrero, David; Tegnér, 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

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

    PubMed

    Cano, Isaac; Selivanov, Vitaly; Gomez-Cabrero, David; Tegnér, 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 (PmO2). Because PmO2 depends on the balance between O2 transport and utilization, we formulated an integrative mathematical model of O2 transport and utilization in skeletal muscle to predict conditions to cause abnormally high ROS generation. Simulations using data from healthy subjects during maximal exercise at sea level reveal little mitochondrial ROS production. However, altitude triggers high mitochondrial ROS production in muscle regions with high metabolic capacity but limited O2 delivery. This altitude roughly coincides with the highest location of permanent human habitation. Above 25,000 ft., more than 90% of exercising muscle is predicted to produce abnormally high levels of ROS, corresponding to the "death zone" in mountaineering.

  4. Mitochondria, reactive oxygen species, and chronological aging: a message from yeast.

    PubMed

    Pan, Yong

    2011-11-01

    As a major intracellular source of reactive oxygen species (ROS), mitochondria are involved in aging and lifespan regulation. Using the yeast chronological aging model, researchers have identified conserved signaling pathways that affect lifespan by modulating mitochondrial functions. Caloric restriction and a genetic mimetic with reduced target of rapamycin signaling globally upregulate the mitochondrial proteome and respiratory functions. Recent discoveries support the notion that an altered mitochondrial proteome induces mitohormesis. Mitohormesis involves a variety of ROS during several growth stages and extends lifespan in yeast and other organisms. Here we recap recent advances in understanding of ROS as signals that decelerate chronological aging in yeast. We also discuss parallels between yeast and worm hypoxic signaling. In sum, this mini-review covers mitochondrial regulation by nutrient-sensing pathways and the complex underlying interactions of ROS, metabolic pathways, and chronological aging.

  5. The Role of Reactive Oxygen Species in Antibiotic-Mediated Killing of Bacteria.

    PubMed

    Van Acker, Heleen; Coenye, Tom

    2017-01-12

    Recently, it was proposed that there is a common mechanism behind the activity of bactericidal antibiotics, involving the production of reactive oxygen species (ROS). However, the involvement of ROS in antibiotic-mediated killing has become the subject of much debate. In the present review, we provide an overview of the data supporting the ROS hypothesis; we also present data that explain the contradictory results often obtained when studying antibiotic-induced ROS production. For this latter aspect we will focus on the importance of taking the experimental setup into consideration and on the importance of some technical aspects of the assays typically used. Finally, we discuss the link between ROS production and toxin-antitoxin modules, and present an overview of implications for treatment.

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

    PubMed

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

    2003-10-03

    Scavenging or quenching of the reactive oxygen species (ROS) involved in oxidative stress has been the subject of many recent studies. Resveratrol, found in various natural food products, has been linked to decreased coronary artery disease and preventing cancer development. The present study measured the effect of resveratrol on several different systems involving the hydroxyl, superoxide, metal/enzymatic-induced, and cellular generated radicals. The rate constant for reaction of resveratrol with the hydroxyl radical was determined, and resveratrol was found to be an effective scavenger of hydroxyl, superoxide, and metal-induced radicals as well as showing antioxidant abilities in cells producing ROS. Resveratrol exhibits a protective effect against lipid peroxidation in cell membranes and DNA damage caused by ROS. Resveratrol was also found to have a significant inhibitory effect on the NF-kappaB signaling pathway after cellular exposure to metal-induced radicals. It was concluded that resveratrol in foods plays an important antioxidant role.

  7. 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

  8. Active Oxygen Species Generator by Low Pressure Silent Discharge and its Application to Water Treatment

    NASA Astrophysics Data System (ADS)

    Tanaka, Masaaki; Ikeda, Akira; Tanimura, Yasuhiro; Ohta, Koji; Yoshiyasu, Hajimu

    We have proposed the new water treatment using the active oxygen species such as an atomic oxygen with the oxidation power that is stronger than ozone. Based on the results of simulations we designed the silent discharge type active oxygen generator with a water ejector, which is operated on the discharge conditions of low pressure of 6.6kPa. and high temperature of about 200°C. The experimental results are as follows. (1) The yield of the active oxygen increases with the increase of the discharge tube temperature and the decrease of the gas pressure. (2) The life time of active oxygen is tens msec. (3) The active oxygen oxidizes efficiently the formic acid compared with ozone. It is assumed from these results that the active oxygen species having a strong oxidation power is generated.

  9. Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species.

    PubMed

    Wang, Hui; Bouzakoura, Soumaya; de Mey, Sven; Jiang, Heng; Law, Kalun; Dufait, Inès; Corbet, Cyril; Verovski, Valeri; Gevaert, Thierry; Feron, Olivier; Van den Berge, Dirk; Storme, Guy; De Ridder, Mark

    2017-05-30

    Auranofin (AF) is an anti-arthritic drug considered for combined chemotherapy due to its ability to impair the redox homeostasis in tumor cells. In this study, we asked whether AF may in addition radiosensitize tumor cells by targeting thioredoxin reductase (TrxR), a critical enzyme in the antioxidant defense system operating through the reductive protein thioredoxin. Our principal findings in murine 4T1 and EMT6 tumor cells are that AF at 3-10 μM is a potent radiosensitizer in vitro, and that at least two mechanisms are involved in TrxR-mediated radiosensitization. The first one is linked to an oxidative stress, as scavenging of reactive oxygen species (ROS) by N-acetyl cysteine counteracted radiosensitization. We also observed a decrease in mitochondrial oxygen consumption with spared oxygen acting as a radiosensitizer under hypoxic conditions. Overall, radiosensitization was accompanied by ROS overproduction, mitochondrial dysfunction, DNA damage and apoptosis, a common mechanism underlying both cytotoxic and antitumor effects of AF. In tumor-bearing mice, a simultaneous disruption of the thioredoxin and glutathione systems by the combination of AF and buthionine sulfoximine was shown to significantly improve tumor radioresponse. In conclusion, our findings illuminate TrxR in cancer cells as an exploitable radiobiological target and warrant further validation of AF in combination with radiotherapy.

  10. Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species

    PubMed Central

    Wang, Hui; Bouzakoura, Soumaya; de Mey, Sven; Jiang, Heng; Law, Kalun; Dufait, Inès; Corbet, Cyril; Verovski, Valeri; Gevaert, Thierry; Feron, Olivier; Van den Berge, Dirk; Storme, Guy; De Ridder, Mark

    2017-01-01

    Auranofin (AF) is an anti-arthritic drug considered for combined chemotherapy due to its ability to impair the redox homeostasis in tumor cells. In this study, we asked whether AF may in addition radiosensitize tumor cells by targeting thioredoxin reductase (TrxR), a critical enzyme in the antioxidant defense system operating through the reductive protein thioredoxin. Our principal findings in murine 4T1 and EMT6 tumor cells are that AF at 3–10 μM is a potent radiosensitizer in vitro, and that at least two mechanisms are involved in TrxR-mediated radiosensitization. The first one is linked to an oxidative stress, as scavenging of reactive oxygen species (ROS) by N-acetyl cysteine counteracted radiosensitization. We also observed a decrease in mitochondrial oxygen consumption with spared oxygen acting as a radiosensitizer under hypoxic conditions. Overall, radiosensitization was accompanied by ROS overproduction, mitochondrial dysfunction, DNA damage and apoptosis, a common mechanism underlying both cytotoxic and antitumor effects of AF. In tumor-bearing mice, a simultaneous disruption of the thioredoxin and glutathione systems by the combination of AF and buthionine sulfoximine was shown to significantly improve tumor radioresponse. In conclusion, our findings illuminate TrxR in cancer cells as an exploitable radiobiological target and warrant further validation of AF in combination with radiotherapy. PMID:28415723

  11. Physiologic and pathologic levels of reactive oxygen species in neat semen of infertile men.

    PubMed

    Desai, Nisarg; Sharma, Rakesh; Makker, Kartikeya; Sabanegh, Edmund; Agarwal, Ashok

    2009-11-01

    To define physiologic levels of reactive oxygen species in infertile men and establish a cutoff value of reactive oxygen species level in neat semen with a high sensitivity and specificity to differentiate infertile men from fertile donors (controls). Reactive oxygen species levels were measured in the neat semen samples (n = 51) from fertile donors and infertile patients (n = 54). Reproductive research laboratory at a tertiary care hospital. Infertile patients from male infertility clinic. Reactive oxygen species measurement in neat semen sample using luminol-based chemiluminescence method, receiver operating characteristic curves. Seminal reactive oxygen species levels, cutoff value, sensitivity and specificity, positive and negative predictive values. The best cutoff value to distinguish between healthy fertile donors and infertile men was 0.0185 x 10(6) counted photons per minute/20 x 10(6) sperm. At this threshold, the specificity was 82% and the sensitivity was 78%. This value can be defined as basal reactive oxygen species level in infertile men. Reactive oxygen species levels in neat semen samples as measured by luminol-based chemiluminescence are a highly specific and sensitive test in the diagnosis of infertility. This test also may help clinicians treat patients with seminal oxidative stress.

  12. CLOCK Promotes Endothelial Damage by Inducing Autophagy through Reactive Oxygen Species

    PubMed Central

    Tang, Xiao; Lin, Changpo; Guo, Daqiao; Qian, Ruizhe; Li, Xiaobo; Shi, Zhenyu; Liu, Jianjun; Li, Xu

    2016-01-01

    A number of recent studies have implicated that autophagy was activated by reactive oxygen species (ROS). Our previous report indicated that CLOCK increased the accumulation of ROS under hypoxic conditions. In this study, we investigated the mechanisms by which CLOCK mediated endothelial damage, focusing on the involvement of oxidative damage and autophagy. Overexpression of CLOCK in human umbilical vein endothelial cells (HUVECs) showed inhibition of cell proliferation and higher autophagosome with an increased expression of Beclin1 and LC3-I/II under hypoxic conditions. In contrast, CLOCK silencing reversed these effects. Interestingly, pretreatment with 3-methyladenine (3-MA) resulted in the attenuation of CLOCK-induced cell autophagy and but did not influence the production of intracellular reactive oxygen species (ROS). Furthermore, Tiron (4,5-dihydroxy-1,3-benzene disulfonic acid-disodium salt), a ROS scavenger, significantly attenuated CLOCK-induced cell autophagy. In addition, we found that overexpression of CLOCK had no significant effects on the production of ROS and expression of Beclin1 and LC3-I/II under normoxic conditions in HUVEC. In this present investigation, our results suggested a novel mechanism of action of CLOCK in HUVECs, opening up the possibility of targeting CLOCK for the treatment of vascular diseases. PMID:28058089

  13. Functional characterization of a reactive oxygen species modulator 1 gene in Litopenaeus vannamei.

    PubMed

    He, Hong-Hui; Chi, Yi-Miao; Yuan, Kai; Li, Xiao-Yun; Weng, Shao-Ping; He, Jian-Guo; Chen, Yi-Hong

    2017-09-06

    Reactive oxygen species (ROS) imparts a dual effect on multicellular organisms, wherein high levels are usually harmful, and low levels could facilitate in combating pathogenic microorganisms; therefore, the regulation of ROS production is critical. Previous studies have suggested that ROS contributes to resistance to the white spot syndrome virus (WSSV) or Vibrio alginolyticus in Litopenaeus vannamei. However, the regulation of ROS metabolism in L. vannamei remains elusive. In the present study, we proved that the overexpression of L. vannamei reactive oxygen species modulator 1 (LvROMO1) increases ROS production in Drosophila Schneider 2 (S2) cells. Real-time RT-PCR analysis indicated that LvROMO1 is induced by WSSV or V. alginolyticus infection and β-glucan or microcystin (MC-LR) injection. Further investigation showed that LvROMO1 responding to MC-LR, thereby inducing hemocytes to undergo apoptosis, and ultimately resulting in hepatopancreatic damage. And LvROMO1 downregulation induced an increase in the cumulative mortality of WSSV-infected shrimp by reducing ROS production and suppressing the expression of antimicrobial peptides genes. The findings of present study suggest that LvROMO1 plays an important role in ROS production in L. vannamei and is involved in innate immunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Methionine oxidation by peroxymonocarbonate, a reactive oxygen species formed from CO2/bicarbonate and hydrogen peroxide.

    PubMed

    Richardson, David E; Regino, Celeste A S; Yao, Huirong; Johnson, Jodie V

    2003-12-15

    Kinetic and thermodynamic evidence is reported for the role of the peroxymonocarbonate ion, HCO4-, as a reactive oxygen species in biology. Peroxymonocarbonate results from the equilibrium reaction of hydrogen peroxide with bicarbonate via the perhydration of CO2. The kinetic parameters for HCO4- oxidation of free methionine have been obtained (k1 = 0.48 +/- 0.08 M(-1)s(-1) by a spectrophotometric initial rate method). At the physiological concentration of bicarbonate in blood ( approximately 25 mM), it is estimated that peroxymonocarbonate formed in equilibrium with hydrogen peroxide will oxidize methionine approximately 2-fold more rapidly than plasma H2O2 itself. As an example of methionine oxidation in proteins, the bicarbonate-catalyzed hydrogen peroxide oxidation of alpha1-proteinase inhibitor (alpha1-PI) has been investigated via its inhibitory effect on porcine pancreatic elastase activity. The second-order rate constant for HCO4- oxidation of alpha1-PI (0.36 +/- 0.06 M(-1)s(-1)) is comparable to that of free methionine, suggesting that methionine oxidation is occurring. Further evidence for methionine oxidation, specifically involving Met358 and Met351 of the alpha1-PI reactive center loop, has been obtained through amino acid analyses and mass spectroscopic analyses of proteolytic digests of the oxidized alpha1-PI. These results strongly suggest that HCO4- should be considered a reactive oxygen species in aerobic metabolism.

  16. Reactive oxygen species controllable non-thermal helium plasmas for evaluation of plasmid DNA strand breaks

    NASA Astrophysics Data System (ADS)

    Young Kim, Jae; Lee, Dong-Hoon; Ballato, John; Cao, Weiguo; Kim, Sung-O.

    2012-11-01

    Non-thermal, oxygen-rich helium plasmas were investigated to achieve an enhanced reactive oxygen species concentration at low voltage driving conditions. A non-thermal plasma device was fabricated based on a theta-shaped tube, and its potential was investigated for use in topological alteration of plasmid DNA. The optical emission spectra of the plasma showed that the oxygen flow affected the plasma properties, even though an oxygen plasma was not produced. The plasmid DNA strand breaks became more significant with the addition of oxygen flow to the helium in a single hollow, theta-shaped tube with other experimental conditions being unchanged.

  17. Oxygen activation by mononuclear nonheme iron dioxygenases involved in the degradation of aromatics.

    PubMed

    Wang, Yifan; Li, Jiasong; Liu, Aimin

    2017-04-01

    Molecular oxygen is utilized in numerous metabolic pathways fundamental for life. Mononuclear nonheme iron-dependent oxygenase enzymes are well known for their involvement in some of these pathways, activating O2 so that oxygen atoms can be incorporated into their primary substrates. These reactions often initiate pathways that allow organisms to use stable organic molecules as sources of carbon and energy for growth. From the myriad of reactions in which these enzymes are involved, this perspective recounts the general mechanisms of aromatic dihydroxylation and oxidative ring cleavage, both of which are ubiquitous chemical reactions found in life-sustaining processes. The organic substrate provides all four electrons required for oxygen activation and insertion in the reactions mediated by extradiol and intradiol ring-cleaving catechol dioxygenases. In contrast, two of the electrons are provided by NADH in the cis-dihydroxylation mechanism of Rieske dioxygenases. The catalytic nonheme Fe center, with the aid of active site residues, facilitates these electron transfers to O2 as key elements of the activation processes. This review discusses some general questions for the catalytic strategies of oxygen activation and insertion into aromatic compounds employed by mononuclear nonheme iron-dependent dioxygenases. These include: (1) how oxygen is activated, (2) whether there are common intermediates before oxygen transfer to the aromatic substrate, and (3) are these key intermediates unique to mononuclear nonheme iron dioxygenases?

  18. 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.

  19. Metal species involved in long distance metal transport in plants

    PubMed Central

    Álvarez-Fernández, Ana; Díaz-Benito, Pablo; Abadía, Anunciación; López-Millán, Ana-Flor; Abadía, Javier

    2014-01-01

    The mechanisms plants use to transport metals from roots to shoots are not completely understood. It has long been proposed that organic molecules participate in metal translocation within the plant. However, until recently the identity of the complexes involved in the long-distance transport of metals could only be inferred by using indirect methods, such as analyzing separately the concentrations of metals and putative ligands and then using in silico chemical speciation software to predict metal species. Molecular biology approaches also have provided a breadth of information about putative metal ligands and metal complexes occurring in plant fluids. The new advances in analytical techniques based on mass spectrometry and the increased use of synchrotron X-ray spectroscopy have allowed for the identification of some metal-ligand species in plant fluids such as the xylem and phloem saps. Also, some proteins present in plant fluids can bind metals and a few studies have explored this possibility. This study reviews the analytical challenges researchers have to face to understand long-distance metal transport in plants as well as the recent advances in the identification of the ligand and metal-ligand complexes in plant fluids. PMID:24723928

  20. 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

  1. Photoactivation of the nematicidal compound alpha-terthienyl from roots of marigolds (Tagetes species). A possible singlet oxygen role.

    PubMed

    Bakker, J; Gommers, F J; Nieuwenhuis, I; Wynberg, H

    1979-03-25

    The nematicidal compound alpha-terthienyl from roots of Tagetes species generates upon irradiation with near ultraviolet light reactive oxygen species on which the in vitro nematicidal activity depends. This system was studied by following the inhibition of glucose-6-phosphate dehydrogenase by photoactivated alpha-terthienyl and protection of the enzyme activity in the absence of oxygen and by various additions. Addition of mannitol, benzoate, superoxide dismutase or catalase did not have any effect nor did H2O2. This suggests that OH., O-.2, and H2O2 are not the reactive oxygen species involved. The enzyme was protected against photoactivated alpha-terthienyl in air-saturated solutions by singlet oxygen quenchers such as histidine, methionine, tryptophan, bovine serum albumin, and NaN3. Furthermore, inactivation of the enzyme was about 3.5 times faster in D2O than in H2O. When alpha-terthienyl in CH2Cl2 was irradiated in the presence of the olefin adamantylideneadamantane, a stable dioxetane was formed which decomposed to adamantanone when heated above its melting point. These results indicate a singlet oxygen-mediated process.

  2. Role of reactive oxygen species in regulation of glucose transport in skeletal muscle during exercise.

    PubMed

    Katz, Abram

    2016-06-01

    Glucose derived from extracellular sources serves as an energy source in virtually all eukaryotic cells, including skeletal muscle. Its contribution to energy turnover increases with exercise intensity up to moderately heavy workloads. However, at very high workloads, the contribution of extracellular glucose to energy turnover is negligible, despite the high rate of glucose transport. Reactive oxygen species (ROS) are involved in the stimulation of glucose transport in isolated skeletal muscle preparations during intense repeated contractions. Consistent with this observation, heavy exercise is associated with significant production of ROS. However, during more mild to moderate stimulation or exercise conditions (in vitro, in situ and in vivo) antioxidants do not affect glucose transport. It is noteworthy that the production of ROS is limited or not observed under these conditions and that the concentration of the antioxidant used was extremely low. The results to date suggest that ROS involvement in activation of glucose transport occurs primarily during intense short-term exercise and that other mechanisms are involved during mild to moderate exercise. What remains puzzling is why ROS-mediated activation of glucose transport would occur under conditions where glucose transport is highest and utilization (i.e. phosphorylation of glucose by hexokinase) is low. Possibly ROS production is involved in priming glucose transport during heavy exercise to accelerate glycogen biogenesis during the initial recovery period after exercise, as well as altering other aspects of intracellular metabolism.

  3. Role of reactive oxygen species in regulation of glucose transport in skeletal muscle during exercise

    PubMed Central

    2016-01-01

    Abstract Glucose derived from extracellular sources serves as an energy source in virtually all eukaryotic cells, including skeletal muscle. Its contribution to energy turnover increases with exercise intensity up to moderately heavy workloads. However, at very high workloads, the contribution of extracellular glucose to energy turnover is negligible, despite the high rate of glucose transport. Reactive oxygen species (ROS) are involved in the stimulation of glucose transport in isolated skeletal muscle preparations during intense repeated contractions. Consistent with this observation, heavy exercise is associated with significant production of ROS. However, during more mild to moderate stimulation or exercise conditions (in vitro, in situ and in vivo) antioxidants do not affect glucose transport. It is noteworthy that the production of ROS is limited or not observed under these conditions and that the concentration of the antioxidant used was extremely low. The results to date suggest that ROS involvement in activation of glucose transport occurs primarily during intense short‐term exercise and that other mechanisms are involved during mild to moderate exercise. What remains puzzling is why ROS‐mediated activation of glucose transport would occur under conditions where glucose transport is highest and utilization (i.e. phosphorylation of glucose by hexokinase) is low. Possibly ROS production is involved in priming glucose transport during heavy exercise to accelerate glycogen biogenesis during the initial recovery period after exercise, as well as altering other aspects of intracellular metabolism. PMID:26791627

  4. Reactive oxygen species (ROS) as early signals in root hair cells responding to rhizobial nodulation factors

    PubMed Central

    Quinto, Carmen

    2008-01-01

    Reactive oxygen species (ROS) are involved in supporting polar growth in pollen tubes, fucoid cells and root hair cells. However, there is limited evidence showing ROS changes during the earliest stages of the interaction between legume roots and rhizobia. We recently reported using Phaseolus vulgaris as a model system, the occurrence of a transient increase of ROS, within seconds, at the tip of actively growing root hair cells after treatment with Nod factors (NFs).1 This transient response is NFs-specific, and clearly distinct from the ROS changes induced by a fungal elicitor, with which sustained increases in ROS signal, is observed. Since ROS levels are transiently elevated after NFs perception, we propose that this ROS response is specific of the symbiotic interaction. Furthermore, the observed ROS changes correlate spatially and temporarily with the reported transient increases in calcium levels suggesting key roles for calcium and ROS during the early NF perception. PMID:19704506

  5. Reactive oxygen species (ROS) as early signals in root hair cells responding to rhizobial nodulation factors.

    PubMed

    Cárdenas, Luis; Quinto, Carmen

    2008-12-01

    Reactive oxygen species (ROS) are involved in supporting polar growth in pollen tubes, fucoid cells and root hair cells. However, there is limited evidence showing ROS changes during the earliest stages of the interaction between legume roots and rhizobia. We recently reported using Phaseolus vulgaris as a model system, the occurrence of a transient increase of ROS, within seconds, at the tip of actively growing root hair cells after treatment with Nod factors (NFs).1 This transient response is NFs-specific, and clearly distinct from the ROS changes induced by a fungal elicitor, with which sustained increases in ROS signal, is observed. Since ROS levels are transiently elevated after NFs perception, we propose that this ROS response is specific of the symbiotic interaction. Furthermore, the observed ROS changes correlate spatially and temporarily with the reported transient increases in calcium levels suggesting key roles for calcium and ROS during the early NF perception.

  6. Role of reactive oxygen species produced by NADPH oxidase in gibberellin biosynthesis during barley seed germination.

    PubMed

    Kai, Kyohei; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Watabe, Gaku; Yuasa, Takashi; Iwaya-Inoue, Mari; Ishibashi, Yushi

    2016-05-03

    NADPH oxidase catalyzes the production of the superoxide anion (O2(-)), a reactive oxygen species (ROS), and regulates the germination of barley (Hordeum vulgare L.). Diphenyleneiodonium (DPI) chloride, an NADPH oxidase inhibitor, delayed barley germination, and exogenous H2O2 (an ROS) partially rescued it. Six enzymes, ent-copalyl diphosphate synthase (CPS), ent-kaurene synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA20-oxidase (GA20ox) and GA3-oxidase (GA3ox), catalyze the transformation of trans-geranylgeranyl diphosphate to active gibberellin, which promotes germination. Exogenous H2O2 promoted the expressions of HvKAO1 and HvGA3ox1 in barley embryos. These results suggest that ROS produced by NADPH oxidase are involved in gibberellin biosynthesis through the regulation of HvKAO1 and HvGA3ox1.

  7. 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

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

    PubMed Central

    Aprioku, Jonah Sydney

    2013-01-01

    The role of free radicals in normal cellular functions and different pathological conditions has been a focus of pharmacological studies in the recent past. Reactive oxygen species (ROS) and free radicals in general are essential for cell signaling and other vital physiological functions; however, excessive amounts can cause alteration in cellular reduction-oxidation (redox) balance, and disrupt normal biological functions. When there is an imbalance between activities of ROS and antioxidant/scavenging defense systems, oxidative stress (OS) occurs. A good number of studies have shown OS is involved in the development of several disease conditions, including male infertility. In the present article, generation of free radicals and their effects, as well as the mechanisms of antioxidant/scavenging defense systems are discussed, with particular focus on the testis. The review also discusses the contribution of OS on testicular dysfunction and briefly focuses on some OS-induced conditions that will alter testicular function. PMID:24551570

  9. 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

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

    PubMed

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

    2016-02-08

    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 (p40(phox) and p47(phox)) 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.

  11. p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis.

    PubMed

    Dolado, Ignacio; Swat, Aneta; Ajenjo, Nuria; De Vita, Gabriella; Cuadrado, Ana; Nebreda, Angel R

    2007-02-01

    p38alpha is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38alpha is not a general inhibitor of oncogenic signaling, but that it specifically modulates transformation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the ROS-induced activation of p38alpha early in the process of transformation, which induces apoptosis and prevents the accumulation of ROS and their carcinogenic effects. Accordingly, highly tumorigenic cancer cell lines have developed a mechanism to uncouple p38alpha activation from ROS production. Our results indicate that oxidative stress sensing plays a key role in the inhibition of tumor initiation by p38alpha.

  12. Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen species and apoptosis of cancer cells.

    PubMed

    Trapasso, Francesco; Pichiorri, Flavia; Gaspari, Marco; Palumbo, Tiziana; Aqeilan, Rami I; Gaudio, Eugenio; Okumura, Hiroshi; Iuliano, Rodolfo; Di Leva, Giampiero; Fabbri, Muller; Birk, David E; Raso, Cinzia; Green-Church, Kari; Spagnoli, Luigi G; Venuta, Salvatore; Huebner, Kay; Croce, Carlo M

    2008-05-16

    Fhit protein is lost in most cancers, its restoration suppresses tumorigenicity, and virus-mediated FHIT gene therapy induces apoptosis and suppresses tumors in preclinical models. We have used protein cross-linking and proteomics methods to characterize a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes Hsp60 and Hsp10 that mediate Fhit stability and may affect import into mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin. Viral-mediated Fhit restoration increases production of intracellular reactive oxygen species, followed by increased apoptosis of lung cancer cells under oxidative stress conditions; conversely, Fhit-negative cells escape apoptosis, carrying serious oxidative DNA damage that may contribute to an increased mutation rate. Characterization of Fhit interacting proteins has identified direct effectors of the Fhit-mediated apoptotic pathway that is lost in most cancers through loss of Fhit.

  13. Computational Models of Reactive Oxygen Species as Metabolic Byproducts and Signal-Transduction Modulators

    PubMed Central

    Pereira, Elizabeth J.; Smolko, Christian M.; Janes, Kevin A.

    2016-01-01

    Reactive oxygen species (ROS) are widely involved in intracellular signaling and human pathologies, but their precise roles have been difficult to enumerate and integrate holistically. The context- and dose-dependent intracellular effects of ROS can lead to contradictory experimental results and confounded interpretations. For example, lower levels of ROS promote cell signaling and proliferation, whereas abundant ROS cause overwhelming damage to biomolecules and cellular apoptosis or senescence. These complexities raise the question of whether the many facets of ROS biology can be joined under a common mechanistic framework using computational modeling. Here, we take inventory of some current models for ROS production or ROS regulation of signaling pathways. Several models captured non-intuitive observations or made predictions that were later verified by experiment. There remains a need for systems-level analyses that jointly incorporate ROS production, handling, and modulation of multiple signal-transduction cascades. PMID:27965578

  14. 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.

  15. Reactive oxygen species mediate compensatory glomerular hypertrophy in rat uninephrectomized kidney.

    PubMed

    Ozeki, Masahito; Nagasu, Hajime; Satoh, Minoru; Namikoshi, Tamehachi; Haruna, Yoshisuke; Tomita, Naruya; Sasaki, Tamaki; Kashihara, Naoki

    2009-09-01

    Hyperfiltration in glomeruli is the most common pathway to progressive renal dysfunction. Moreover, reduction of renal mass by unilateral nephrectomy results in an immediate increase in glomerular flow to the remnant kidney, followed by compensatory glomerular hypertrophy. Reactive oxygen species (ROS) are involved in renal hypertrophic responses; however, the role of ROS in compensatory glomerular hypertrophy remains unclear. Therefore, this role was investigated in the present study. Wistar rats were randomly placed into two groups: uninephrectomized rats (Nx) and uninephrectomized rats treated with tempol (Nx + TP). The glomerular volume increased in the Nx 1 week after surgery, but was significantly suppressed in the Nx + TP. Levels of phospho-Akt and phospho-ribosomal protein S6, which are critical for cell growth and hypertrophy, were markedly increased in the glomeruli of the Nx, while tempol treatment almost abolished the activation of these proteins. These results suggest that ROS have important roles in compensatory hypertrophy in glomeruli.

  16. The role of mitochondria in reactive oxygen species metabolism and signaling.

    PubMed

    Starkov, Anatoly A

    2008-12-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  18. Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells.

    PubMed

    Li, Yang; Liu, Xiaokang; Jiang, Dan; Lin, Yingjia; Wang, Yushi; Li, Qing; Liu, Linlin; Jin, Ying-Hua

    2016-09-01

    Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose-dependent manner. Addition of antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells.

  19. 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.

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

    SciTech Connect

    Arif, J.M.; Khan, S.G.; Ashquin, M.; Rahman, Q. )

    1993-05-01

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

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

    PubMed

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

    2014-03-01

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

  2. Pomegranate-Derived Polyphenols Reduce Reactive Oxygen Species Production via SIRT3-Mediated SOD2 Activation

    PubMed Central

    Zhao, Chong; Sakaguchi, Takenori; Fujita, Kosuke; Ito, Hideyuki; Nishida, Norihisa; Nagatomo, Akifumi; Tanaka-Azuma, Yukimasa

    2016-01-01

    Pomegranate-derived polyphenols are expected to prevent life-style related diseases. In this study, we evaluated the ability of 8 pomegranate-derived polyphenols, along with other polyphenols, to augment SIRT3, a mammalian SIR2 homolog localized in mitochondria. We established a system for screening foods/food ingredients that augment the SIRT3 promoter in Caco-2 cells and identified 3 SIRT3-augmenting pomegranate-derived polyphenols (eucalbanin B, pomegraniin A, and eucarpanin T1). Among them, pomegraniin A activated superoxide dismutase 2 (SOD2) through SIRT3-mediated deacetylation, thereby reducing intracellular reactive oxygen species. The other SIRT3-augmenting polyphenols tested also activated SOD2, suggesting antioxidant activity. Our findings clarify the underlying mechanisms involved in the antioxidant activity of pomegraniin A. PMID:27840668

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

    PubMed Central

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

    2014-01-01

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

  4. 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...

  5. 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...

  6. 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...

  7. 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...

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

    PubMed

    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.

  9. Mitochondrial Structure and Reactive Oxygen Species in Mammary Oncogenesis

    DTIC Science & Technology

    2007-04-01

    for the subunits of this Complex responsible for the hereditary paraganglioma and pheochromocytoma (2- 4,12,13,30,31,32) suggest that Complex II... physiologic equilibrium or homeostasis (48). The cell might use such ROS homeostatic balance as one of its oxygen sensing mechanisms (9,11,26). The...activities. Hence, the transgene expression could be heavily dependent on these physiological changes that require quite lengthy experimental and/or

  10. The Effect of Oxygen Potential on the Sulfide Capacity for Slags Containing Multivalent Species

    NASA Astrophysics Data System (ADS)

    Allertz, Carl; Selleby, Malin; Sichen, Du

    2016-10-01

    The dependence of sulfide capacity on the oxygen partial pressure for slags containing multivalent species was investigated experimentally using a slag containing vanadium oxide. Copper-slag equilibration experiments were carried out at 1873 K (1600 °C) in the approximate oxygen partial pressure range 10-15.4 to 10-9 atm. The sulfide capacity was found to be strongly dependent on the oxygen potential in this slag system, increasing with the oxygen partial pressure. The sulfide capacity changed by more than two orders of magnitude over the oxygen partial pressure range. The effect of changing oxygen partial pressure was found to be much greater than the effect of changing slag composition at a fixed oxygen partial pressure.

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

    SciTech Connect

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

    1983-11-01

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

  12. 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

  13. Species-level variability in extracellular production rates of reactive oxygen species by diatoms

    NASA Astrophysics Data System (ADS)

    Schneider, Robin; Roe, Kelly; Hansel, Colleen; Voelker, Bettina

    2016-03-01

    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 x 10-16 mol cell-1 hr-1, while H2O2 production rates ranged from undetectable to 3.4 x 10-16 mol cell-1 hr-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 H2O¬2 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

  14. Characterization of the Oxygen Transmission Rate of Oak Wood Species Used in Cooperage.

    PubMed

    Del Alamo-Sanza, María; Cárcel, Luis Miguel; Nevares, Ignacio

    2017-01-25

    The oxygen that wine receives while aged in barrels is of interest because it defines the reactions that occur during aging and, therefore, the final properties of the wine. This study is intended to make up for the lack of information concerning the oxygen permeability of eight different woods of Quercus alba L. and Quercus petraea (Matt.) Liebl. commonly used. In addition, it shows how oxygen transfer evolves with the liquid contact time during testing under similar aging conditions to those in wine barrels. French oak woods permitted a higher oxygenation rate than American ones in all cases. A decrease in the oxygen entry caused by impregnation of the wood during the process was observed in all of the species studied. This process is determined by the thickness of the flooded wood layer containing free water, although differently in the two species, possibly due to the anatomical structure and the logging process for each.

  15. 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

  16. Marine species in ambient low-oxygen regions subject to double jeopardy impacts of climate change.

    PubMed

    Stortini, Christine H; Chabot, Denis; Shackell, Nancy L

    2017-06-01

    We have learned much about the impacts of warming on the productivity and distribution of marine organisms, but less about the impact of warming combined with other environmental stressors, including oxygen depletion. Also, the combined impact of multiple environmental stressors requires evaluation at the scales most relevant to resource managers. We use the Gulf of St. Lawrence, Canada, characterized by a large permanently hypoxic zone, as a case study. Species distribution models were used to predict the impact of multiple scenarios of warming and oxygen depletion on the local density of three commercially and ecologically important species. Substantial changes are projected within 20-40 years. A eurythermal depleted species already limited to shallow, oxygen-rich refuge habitat (Atlantic cod) may be relatively uninfluenced by oxygen depletion but increase in density within refuge areas with warming. A more stenothermal, deep-dwelling species (Greenland halibut) is projected to lose ~55% of its high-density areas under the combined impacts of warming and oxygen depletion. Another deep-dwelling, more eurythermal species (Northern shrimp) would lose ~4% of its high-density areas due to oxygen depletion alone, but these impacts may be buffered by warming, which may increase density by 8% in less hypoxic areas, but decrease density by ~20% in the warmest parts of the region. Due to local climate variability and extreme events, and that our models cannot project changes in species sensitivity to hypoxia with warming, our results should be considered conservative. We present an approach to effectively evaluate the individual and cumulative impacts of multiple environmental stressors on a species-by-species basis at the scales most relevant to managers. Our study may provide a basis for work in other low-oxygen regions and should contribute to a growing literature base in climate science, which will continue to be of support for resource managers as climate change

  17. Contribution of reactive oxygen species to UV-B-induced damage in bacteria.

    PubMed

    Santos, Ana L; Gomes, Newton C M; Henriques, Isabel; Almeida, Adelaide; Correia, António; Cunha, Ângela

    2012-12-05

    The present work aimed to identify the reactive oxygen species (ROS) produced during UV-B exposure and their biochemical targets, in a set of bacterial isolates displaying different UV susceptibilities. For that, specific exogenous ROS scavengers (catalase/CAT, superoxide dismutase/SOD, sodium azide and mannitol) were used. Biological effects were assessed from total bacterial number, colony counts and heterotrophic activity (glucose uptake and respiration). DNA strand breakage, ROS generation, oxidative damage to proteins and lipids were used as markers of oxidative stress. Sodium azide conferred a statistically significant protection in terms of lipid oxidation and cell survival, suggesting that singlet oxygen might play an important role in UV-B induced cell inactivation. Mannitol exerted a significant protection against DNA strand breakage and protein carbonylation, assigning hydroxyl radicals to DNA and protein damage. The addition of exogenous CAT and SOD significantly protected the capacity for glucose uptake and respiration, suggesting that superoxide and H(2)O(2) are involved in the impairment of activity during UV-B exposure. The observation that amendment with ROS scavengers can sometimes also exert a pro-oxidant effect suggests that the intracellular oxidant status of the cell ultimately determines the efficiency of antioxidant defenses.

  18. Reactive oxygen species-mediated cardiac-reperfusion injury: Mechanisms and therapies.

    PubMed

    Bagheri, Fereshte; Khori, Vahid; Alizadeh, Ali Mohammad; Khalighfard, Solmaz; Khodayari, Saeed; Khodayari, Hamid

    2016-11-15

    Reperfusion injury is an inherent response to the restoration of blood flow after ischemia. It is a complex process involving numerous mechanisms occurring in the intracellular and extracellular environments, and it is mediated in part by reactive oxygen species (ROS). The imbalance between the cellular formation of free radicals and cells' capacity to defend against them can cause cardiac tissue injuries. In this context, ROS play an essential role in both the organ injury and repair processes. After reperfusion, infiltration into the myocardium of inflammatory leucocytes, such as macrophages and neutrophils, causes further ROS production beyond the initiation of the inflammatory cascade. In this case, ROS overproduction is crucial in cardiac injury, and it can increase the complications related to cardiac reperfusion. In myocardial tissue, ROS can be produced from several sources, such as xanthine oxidase, cytochrome oxidase, cyclooxygenase, mediated unsaturated fatty acid oxidation, oxidation of catecholamines, mitochondrial oxidation, activation of leukocyte nicotinamide adenine dinucleotide phosphate oxidase, iron release, and reduction-oxidation reaction cycling; all of these sources reduce molecular oxygen in the reperfused myocardium. This review discusses about the molecular and therapeutic aspects of cardiac-reperfusion injuries generated by ROS. Experimental and clinical evidence with respect to the use of ischemic preconditioning, Ca(2+), nitric oxide, and conventional antioxidants in cardiac-reperfusion injury are summarized, and causal therapy approaches with various antioxidants are discussed.

  19. Sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan

    PubMed Central

    Patrick, Alison; Seluanov, Michael; Hwang, Chaewon; Tam, Jonathan; Khan, Tanya; Morgenstern, Ari; Wiener, Lauren; Vazquez, Juan M.; Zafar, Hiba; Wen, Robert; Muratkalyeva, Malika; Doerig, Katherine; Zagorulya, Maria; Cole, Lauren; Catalano, Sophia; Lobo Ladd, Aliny AB; Coppi, A. Augusto; Coşkun, Yüksel; Tian, Xiao; Ablaeva, Julia; Nevo, Eviatar; Gladyshev, Vadim N.; Zhang, Zhengdong D.; Vijg, Jan; Seluanov, Andrei; Gorbunova, Vera

    2016-01-01

    Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild-caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species' lifespan. PMID:27163160

  20. Cortisol Induces Reactive Oxygen Species Through a Membrane Glucocorticoid Receptor in Rainbow Trout Myotubes.

    PubMed

    Espinoza, Marlen B; Aedo, Jorge E; Zuloaga, Rodrigo; Valenzuela, Cristian; Molina, Alfredo; Valdés, Juan A

    2017-04-01

    Cortisol is an essential regulator of neuroendocrine stress responses in teleosts. Cortisol predominantly affects target tissues through the genomic pathway, which involves interacting with cytoplasmic glucocorticoid receptors, and thereby, modulating stress-response gene expressions. Cortisol also produces rapid effects via non-genomic pathways, which do not involve gene transcription. Although cortisol-mediated genomic pathways are well documented in teleosts, non-genomic pathways are not fully understood. Moreover, no studies have focused on the contribution of non-genomic cortisol pathways in compensatory stress responses in fish. In this study, rainbow trout (Oncorhynchus mykiss) skeletal myotubes were stimulated with physiological concentrations of cortisol and cortisol-BSA, a membrane-impermeable agent, resulting in an early induction of reactive oxygen species (ROS). This production was not suppressed by transcription or translation inhibitors, suggesting non-genomic pathway involvement. Moreover, myotube preincubation with RU486 and NAC completely suppressed cortisol- and cortisol-BSA-induced ROS production. Subcellular fractionation analysis revealed the presence of cell membrane glucocorticoid receptors. Finally, cortisol-BSA induced a significant increase in ERK1/2 and CREB phosphorylation, as well as in CREB-dependent transcriptional activation of the pgc1a gene expression. The obtained results strongly suggest that cortisol acts through a non-genomic glucocorticoid receptor-mediated pathway to induce ROS production and contribute to ERK/CREB/PGC1-α signaling pathway activation as stress compensation mechanisms. J. Cell. Biochem. 118: 718-725, 2017. © 2016 Wiley Periodicals, Inc.

  1. Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis.

    PubMed

    Kountouras, Jannis; Boziki, Marina; Polyzos, Stergios A; Katsinelos, Panagiotis; Gavalas, Emmanouel; Zeglinas, Christos; Tzivras, Dimitri; Romiopoulos, Iordanis; Giorgakis, Nikolaos; Anastasiadou, Kyriaki; Vardaka, Elizabeth; Kountouras, Constantinos; Kazakos, Evangelos; Xiromerisiou, Georgia; Dardiotis, Efthimios; Deretzi, Georgia

    2017-01-01

    Helicobacter pylori (H. pylori) induces reactive oxygen species (ROS) production that contribute to pathogenesis of a variety of H. pylori-related gastric diseases, as shown in animal and human studies. Helicobacter pylori infection is also associated with variety of systemic extragastric diseases in which H. pylori-related ROS production might also be involved in the pathogenesis of these systemic conditions. We proposed that Hp-related ROS may play a crucial role in the pathophysiology of Hp-related systemic diseases including Alzheimer's disease, multiple sclerosis, glaucoma and other relative neurodegenerative diseases, thereby suggesting introduction of relative ROS scavengers as therapeutic strategies against these diseases which are among the leading causes of disability and are associated with a large public health global burden. Moreover, we postulated that H. pylori-related ROS might also be involved in the pathogenesis of extragastric common malignancies, thereby suggesting that H. pylori eradication might inhibit the development or delay the progression of aforementioned diseases. However, large-scale future studies are warranted to elucidate the proposed pathophysiological mechanisms, including H. pylori-related ROS, involved in H. pylori-associated systemic and malignant conditions.

  2. 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.

  3. Reactive oxygen species in Hevea brasiliensis latex and relevance to Tapping Panel Dryness.

    PubMed

    Zhang, Yi; Leclercq, Julie; Montoro, Pascal

    2016-11-29

    Environmental stress can lead to oxidative stress resulting from an increase in reactive oxygen species (ROS) and involves redox adjustments. Natural rubber is synthesized in laticifers, which is a non-photosynthetic tissue particularly prone to oxidative stress. This paper reviews the current state of knowledge on the ROS production and ROS-scavenging systems in laticifers. These regulations have been the subject of intense research into a physiological syndrome, called Tapping Panel Dryness (TPD), affecting latex production in Hevea brasiliensis In order to prevent TPD occurrence, monitoring thiol content appeared to be a crucial factor of latex diagnosis. Thiols, ascorbate and γ-tocotrienol are the major antioxidants in latex. They are involved in membrane protection from ROS and likely have an effect on the quality of raw rubber. Some transcription factors might play a role in the redox regulatory network in Hevea, in particular ethylene response factors, which have been the most intensively studied given the role of ethylene on rubber production. Current challenges for rubber research and development with regard to redox systems will involve improving antioxidant capacity using natural genetic variability.

  4. Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.

    PubMed

    Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarães, D D

    2011-09-01

    Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.

  5. Miltefosine-unresponsive Leishmania donovani has a greater ability than miltefosine-responsive L. donovani to resist reactive oxygen species.

    PubMed

    Das, Mousumi; Saudagar, Prakash; Sundar, Shyam; Dubey, Vikash K

    2013-10-01

    Resistance of Leishmania parasites to miltefosine, which is only available oral drug, is a great concern. We have analyzed global gene expression profiles of miltefosine-unresponsive and miltefosine-responsive Leishmania donovani in order to understand the various metabolic processes involved in miltefosine drug resistance. The microarray data clearly indicated a role of oxidative metabolism in miltefosine resistance. Furthermore, fluorescence microscopy experiments suggested that miltefosine-unresponsive L. donovani resists the accumulation of reactive oxygen species and subsequent mitochondrial membrane damage leading to apoptotic death. In contrast, in miltefosine-responsive L. donovani, the accumulation of reactive oxygen species causes apoptotic death. Overall, this study provides fundamental insights into miltefosine resistance in L. donovani.

  6. 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.

  7. Roles of reactive oxygen and nitrogen species in pain.

    PubMed

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

    2011-09-01

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

  8. 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

  9. Unexpected Sources of Reactive Oxygen Species in Natural Water

    NASA Astrophysics Data System (ADS)

    Kahan, T.; Grossman, J. N.

    2016-12-01

    We report novel formation methods of hydroxyl radicals (OH) and singlet oxygen (1O2) relevant to surface waters and aqueous aerosols. In one set of studies, we demonstrate that 1O2 can be produced photochemically in aqueous solutions containing polycyclic aromatic hydrocarbons (PAHs) and halide ions under environmentally relevant conditions. This process may be important to oxidizing capacity and pollutant fate in saline waters including oceans and aqueous aerosols. In a second set of studies, we present a potentially important dark radical source. The Fenton reaction is a major dark radical source in natural waters, but it is negligibly slow at neutral pH due to the insolubility of Fe(III). We demonstrate that OH production rates from the dark Fenton reaction at pH 7 can be greatly increased by the iron-reducing bacterium Shewanella Oneidensis (SO). Our results suggest that OH production (and therefore oxidizing capacity) may be much greater than currently expected in dark circumneutral waters containing iron-reducing bacteria.

  10. 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.

  11. 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.

    2012-10-01

    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 rf driven atmospheric-pressure helium-oxygen mixture plasmas (helium with 5000 ppm admixture of oxygen) for wide air impurity levels of 0-500 ppm with relative humidities of from 0 to 100% using a zero-dimensional, time-dependent global model. Comparisons are made with experimental measurements in an rf driven micro-scale atmospheric pressure plasma jet and with one-dimensional semi-kinetic simulations of the same plasma jet. The evolution of species concentration is described for reactive oxygen species, metastable species, radical species and positively- and negatively-charged ions (and its clusters). Effects of the air impurity containing water humidity on electronegativity and chemical activity are clarified with particular emphasis on reactive oxygen species.

  12. Modulation of reactive oxygen species by salicylic acid in Arabidopsis seed germination under high salinity.

    PubMed

    Lee, Sangmin; Park, Chung-Mo

    2010-12-01

    Potential roles of salicylic acid (SA) on seed germination have been explored in many plant species. However, it is still controversial how SA regulates seed germination, mainly because the results have been somewhat variable, depending on plant genotypes used and experimental conditions employed. We found that SA promotes seed germination under high salinity in Arabidopsis. Seed germination of the sid2 mutant, which has a defect in SA biosynthesis, is hypersensitive to high salinity, but the inhibitory effects are reduced in the presence of physiological concentrations of SA. Abiotic stresses, including high salinity, impose oxidative stress on plants. Endogenous contents of H(2)O(2) are higher in the sid2 mutant seeds. However, exogenous application of SA reduces endogenous level of reactive oxygen species (ROS), indicating that SA is involved in plant responses to ROS-mediated damage under abiotic stress conditions. Gibberellic acid (GA), a plant hormone closely associated with seed germination, also reverses the inhibitory effects of high salinity on seed germination and seedling establishment. Under high salinity, GA stimulates SA biosynthesis by inducing the SID2 gene. Notably, SA also induces genes encoding GA biosynthetic enzymes. These observations indicate that SA promotes seed germination under high salinity by modulating antioxidant activity through signaling crosstalks with GA.

  13. The Role of External and Matrix pH in Mitochondrial Reactive Oxygen Species Generation*

    PubMed Central

    Selivanov, Vitaly A.; Zeak, Jennifer A.; Roca, Josep; Cascante, Marta; Trucco, Massimo; Votyakova, Tatyana V.

    2008-01-01

    Reactive oxygen species (ROS) generation in mitochondria as a side product of electron and proton transport through the inner membrane is important for normal cell operation as well as development of pathology. Matrix and cytosol alkalization stabilizes semiquinone radical, a potential superoxide producer, and we hypothesized that proton deficiency under the excess of electron donors enhances reactive oxygen species generation. We tested this hypothesis by measuring pH dependence of reactive oxygen species released by mitochondria. The experiments were performed in the media with pH varying from 6 to 8 in the presence of complex II substrate succinate or under more physiological conditions with complex I substrates glutamate and malate. Matrix pH was manipulated by inorganic phosphate, nigericine, and low concentrations of uncoupler or valinomycin. We found that high pH strongly increased the rate of free radical generation in all of the conditions studied, even when ΔpH = 0 in the presence of nigericin. In the absence of inorganic phosphate, when the matrix was the most alkaline, pH shift in the medium above 7 induced permeability transition accompanied by the decrease of ROS production. ROS production increase induced by the alkalization of medium was observed with intact respiring mitochondria as well as in the presence of complex I inhibitor rotenone, which enhanced reactive oxygen species release. The phenomena revealed in this report are important for understanding mechanisms governing mitochondrial production of reactive oxygen species, in particular that related with uncoupling proteins. PMID:18687689

  14. Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables.

    PubMed

    Wilcox, Christopher S

    2012-02-01

    Plasma levels of asymmetric dimethylarginine or markers of reactive oxygen species are increased in subjects with risk factors for cardiovascular disease or chronic kidney disease. We tested the hypothesis that reactive oxygen species generate cellular asymmetric dimethylarginine that together cause endothelial dysfunction that underlies the risk of subsequent disease. Rat preglomerular vascular smooth muscle cells transfected with p22(phox) had increased NADPH oxidase activity, enhanced activity and expression of protein arginine methyltransferase, and reduced activity and protein expression of dimethylarginine dimethylaminotransferase and of cationic amino acid transferase 1 resulting in increased cellular levels of asymmetric dimethylarginine. Rats infused with angiotensin II had oxidative stress. The endothelial function of their mesenteric arterioles was changed from vasodilatation to vasoconstriction, accompanied by increased vascular asymmetric dimethylarginine. All of these changes were prevented by Tempol. In vivo silencing of dimethylarginine dimethylaminotransferase 1 increased plasma levels of asymmetric dimethylarginine, whereas silencing of dimethylarginine dimethylaminotransferase 2 impaired endothelial function. We suggest that initiation factors, such as angiotensin II, expressed in blood vessels or tissues of subjects with cardiovascular and kidney disease risk factors generate reactive oxygen species from NADPH oxidase that enhances cellular asymmetric dimethylarginine in an amplification loop. This leads to adverse changes in vascular and organ functions, as a consequence of reduced tissue levels of NO and increased reactive oxygen species. Thus, we conclude that reactive oxygen species and asymmetric dimethylarginine form a tightly coupled amplification system that translates cardiovascular/kidney risk into overt disease.

  15. The role of external and matrix pH in mitochondrial reactive oxygen species generation.

    PubMed

    Selivanov, Vitaly A; Zeak, Jennifer A; Roca, Josep; Cascante, Marta; Trucco, Massimo; Votyakova, Tatyana V

    2008-10-24

    Reactive oxygen species (ROS) generation in mitochondria as a side product of electron and proton transport through the inner membrane is important for normal cell operation as well as development of pathology. Matrix and cytosol alkalization stabilizes semiquinone radical, a potential superoxide producer, and we hypothesized that proton deficiency under the excess of electron donors enhances reactive oxygen species generation. We tested this hypothesis by measuring pH dependence of reactive oxygen species released by mitochondria. The experiments were performed in the media with pH varying from 6 to 8 in the presence of complex II substrate succinate or under more physiological conditions with complex I substrates glutamate and malate. Matrix pH was manipulated by inorganic phosphate, nigericine, and low concentrations of uncoupler or valinomycin. We found that high pH strongly increased the rate of free radical generation in all of the conditions studied, even when DeltapH=0 in the presence of nigericin. In the absence of inorganic phosphate, when the matrix was the most alkaline, pH shift in the medium above 7 induced permeability transition accompanied by the decrease of ROS production. ROS production increase induced by the alkalization of medium was observed with intact respiring mitochondria as well as in the presence of complex I inhibitor rotenone, which enhanced reactive oxygen species release. The phenomena revealed in this report are important for understanding mechanisms governing mitochondrial production of reactive oxygen species, in particular that related with uncoupling proteins.

  16. Activation of sperm EGFR by light irradiation is mediated by reactive oxygen species.

    PubMed

    Shahar, Shiran; Hillman, Pnina; Lubart, Rachel; Ickowicz, Debby; Breitbart, Haim

    2014-01-01

    To acquire fertilization competence, spermatozoa must undergo several biochemical and motility changes in the female reproductive tract, collectively called capacitation. Actin polymerization and the development of hyperactivated motility (HAM) are part of the capacitation process. In a recent study, we showed that irradiation of human sperm with visible light stimulates HAM through a mechanism involving reactive-oxygen-species (ROS), Ca(2+) influx, protein kinases A (PKA), and sarcoma protein kinase (Src). Here, we showed that this effect of light on HAM is mediated by ROS-dependent activation of the epidermal growth factor receptor (EGFR). Interestingly, ROS-mediated HAM even when the EGFR was activated by EGF, the physiological ligand of EGFR. Light irradiation stimulated ROS-dependent actin polymerization, and this effect was abrogated by PBP10, a peptide which activates the actin-severing protein, gelsolin, and causes actin-depolymerization in human sperm. Light-stimulated tyrosine phosphorylation of Src-dependent gelsolin, resulting in enhanced HAM. Thus, light irradiation stimulates HAM through a mechanism involving Src-mediated actin polymerization. Light-stimulated HAM and in vitro-fertilization (IVF) rate in mouse sperm, and these effects were mediated by ROS and EGFR. In conclusion, we show here that irradiation of sperm with visible light, enhances their fertilization capacity via a mechanism requiring ROS, EGFR and HAM.

  17. Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species

    PubMed Central

    Perrelli, Maria-Giulia; Pagliaro, Pasquale; Penna, Claudia

    2011-01-01

    Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction (AMI). However reperfusion is responsible for additional myocardial damage, which likely involves opening of the mitochondrial permeability transition pore (mPTP). In reperfusion injury, mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability. Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species (ROS). Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning, obtained with brief intermittent ischemia or with pharmacological agents. These pathways converge on a common target, the mitochondria, to preserve their function after ischemia/reperfusion. The present review discusses the role of mitochondria in cardioprotection, especially the involvement of adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP. Ischemic postconditioning has emerged as a new way to target the mitochondria, and to drastically reduce lethal reperfusion injury. Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects, and an interesting alternative is pharmacological postconditioning. In fact ischemic postconditioning and the mPTP desensitizer, cyclosporine A, have been shown to induce comparable protection in AMI patients. PMID:21772945

  18. Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production

    PubMed Central

    Spencer, Nicholas G.; Schilling, Tom; Miralles, Francesc; Eder, Claudia

    2016-01-01

    Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology. PMID:27598576

  19. Resveratrol attenuates azidothymidine-induced cardiotoxicity by decreasing mitochondrial reactive oxygen species generation in human cardiomyocytes

    PubMed Central

    GAO, RACHEL YUE; MUKHOPADHYAY, PARTHA; MOHANRAJ, RAJESH; WANG, HUA; HORVÁTH, BÉLA; YIN, SHI; PACHER, PÁL

    2011-01-01

    Nucleotide reverse transcriptase inhibitors, such as zidovudine (azidothymidine, AZT) and stavudine, represent a class of approved antiretroviral agents for highly active antiretroviral therapy, which prolongs the life expectancy of patients infected with human-immunodeficiency virus. Unfortunately, the use of these drugs is associated with known toxicities in the liver, skeletal muscle, heart and other organs, which may involve increased reactive oxygen species (ROS) generation, among other mechanisms. Resveratrol is a polyphenolic plant-derived antioxidant abundantly found in certain grapes, roots, berries, peanuts and red wine. This study, using primary human cardiomyocytes, evaluated the effects of AZT and pre-treatment with resveratrol on mitochondrial ROS generation and the cell death pathways. AZT induced concentration-dependent cell death, involving both caspase-3 and -7 and poly(ADP-ribose) polymerase activation, coupled with increased mitochondrial ROS generation in human cardiomyocytes. These effects of AZT on mitochondrial ROS generation and cell death may be attenuated by resveratrol pre-treatment. The results demonstrate that mitochondrial ROS generation plays a pivotal role in the cardiotoxicity of AZT in human cardiomyocytes, and resveratrol may provide a potential strategy to attenuate these pathological alterations, which are associated with widely used antiretroviral therapy. PMID:21461578

  20. Resveratrol attenuates azidothymidine-induced cardiotoxicity by decreasing mitochondrial reactive oxygen species generation in human cardiomyocytes.

    PubMed

    Gao, Rachel Yue; Mukhopadhyay, Partha; Mohanraj, Rajesh; Wang, Hua; Horváth, Béla; Yin, Shi; Pacher, Pál

    2011-01-01

    Nucleotide reverse transcriptase inhibitors, such as zidovudine (azidothymidine, AZT) and stavudine, represent a class of approved antiretroviral agents for highly active antiretroviral therapy, which prolongs the life expectancy of patients infected with human-immunodeficiency virus. Unfortunately, the use of these drugs is associated with known toxicities in the liver, skeletal muscle, heart and other organs, which may involve increased reactive oxygen species (ROS) generation, among other mechanisms. Resveratrol is a polyphenolic plant-derived antioxidant abundantly found in certain grapes, roots, berries, peanuts and red wine. This study, using primary human cardiomyocytes, evaluated the effects of AZT and pre-treatment with resveratrol on mitochondrial ROS generation and the cell death pathways. AZT induced concentration-dependent cell death, involving both caspase-3 and -7 and poly(ADP-ribose) polymerase activation, coupled with increased mitochondrial ROS generation in human cardiomyocytes. These effects of AZT on mitochondrial ROS generation and cell death may be attenuated by resveratrol pre-treatment. The results demonstrate that mitochondrial ROS generation plays a pivotal role in the cardiotoxicity of AZT in human cardiomyocytes, and resveratrol may provide a potential strategy to attenuate these pathological alterations, which are associated with widely used antiretroviral therapy.

  1. Nitric Oxide and Reactive Oxygen Species Mediate Metabolic Changes in Barley Seed Embryo during Germination.

    PubMed

    Ma, Zhenguo; Marsolais, Frédéric; Bykova, Natalia V; Igamberdiev, Abir U

    2016-01-01

    The levels of nitric oxide (NO) and reactive oxygen species (ROS), ATP/ADP ratios, reduction levels of ascorbate and glutathione, expression of the genes encoding proteins involved in metabolism of NO and activities of the enzymes involved in fermentation and in metabolism of NO and ROS were studied in the embryos of germinating seeds of two barley (Hordeum vulgare L.) cultivars differing in dormancy level. The level of NO production continuously increased after imbibition while the level of nitrosylated SH-groups in proteins increased. This corresponded to the decrease of free SH-groups in proteins. At early stage of germination (0-48 h post imbibition) the genes encoding class 1 phytoglobin (the protein scavenging NO) and S-nitrosoglutathione reductase (scavenging S-nitrosoglutathione) were markedly expressed. More dormant cultivar exhibited lower ATP/ADP and ascorbate/dehydroascorbate ratios and lower lactate and alcohol dehydrogenase activities, while the production of NO and nitrosylation of proteins was higher as compared to the non-dormant cultivar. The obtained data indicate that at the onset of germination NO is actively generated causing nitrosylation of SH-groups and a switch from respiration to fermentation. After radicle protrusion the metabolism changes in a more reducing type as recorded by ratio of reduced and oxidized glutathione and ascorbate. The turnover of NO by the scavenging systems (phytoglobin, S-nitrosoglutathione reductase and interaction with ROS) might contribute to the maintenance of redox and energy balance of germinating seeds and lead to alleviation of dormancy.

  2. 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

  3. 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.

  4. [Impact of biologically important anions on reactive oxygen species formation in water under the effect of non-ionizing physical agents].

    PubMed

    Gudkov, S V; Ivanov, V E; Karp, O É; Chernikov, A V; Belosludtsev, K N; Bobylev, A G; Astashev, M E; Gapeev, A B; Bruskov, V I

    2014-01-01

    The influence of biologically relevant anions (succinate, acetate, citrate, chloride, bicarbonate, hydroorthophosphate, dihydroorthophosphate, nitrite, nitrate) on the formation of hydrogen peroxide and hydroxyl radicals in water was studied under the effect of non-ionizing radiation: heat, laser light with a wavelength of 632.8 nm, corresponding to the maximum absorption of molecular oxygen, and electromagnetic radiation of extremely high frequencies. It has been established that various anions may both inhibit the formation of reactive oxygen species and increase it. Bicarbonate and sulfate anions included in the biological fluids' and medicinal mineral waters have significant, but opposite effects on reactive oxygen species production. Different molecular mechanisms of reactive oxygen species formation are considered under the action of the investigated physical factors involving these anions, which may influence the biological processes by signal-regulatory manner and provide a healing effect in physical therapy.

  5. 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.

  6. Voltage, reactive oxygen species and the influx of calcium

    PubMed Central

    Mortimer, Jennifer C; Laohavisit, Anuphon; Miedema, Henk

    2008-01-01

    The apical plasma membrane of young Arabidopsis root hairs has recently been found to contain a depolarisation-activated Ca2+ channel, in addition to one activated by hyperpolarisation. The depolarisation-activated Ca2+ channel may function in signalling but the possibility that the root hair apical plasma membrane voltage may oscillate between a hyperpolarized and depolarized state suggests a role in growth control. Plant NADPH oxidase activity has yet to be considered in models of oscillatory voltage or ionic flux despite its predicted electrogenicity and voltage dependence. Activity of root NADPH oxidase was found to be stimulated by restricting Ca2+ influx, suggesting that these enzymes are involved in sensing Ca2+ entry into cells. PMID:19704832

  7. Effects of coordination number of Au catalyst on oxygen species and their catalytic roles

    NASA Astrophysics Data System (ADS)

    Ouyang, Gen; Zhu, Kong-Jie; Zhang, Lei; Cui, Peng-Fei; Teng, Bo-Tao; Wen, Xiao-Dong

    2016-11-01

    To explore the effects of coordination number of Au nanoparticles on oxygen species and their catalytic roles is very important in gold catalysis. Based on the systematic study of oxygen adsorption on Au(997) by density functional theory calculation, the quantitative correlation for different oxygen species with coverage and Au coordination number is established in theory. The only O adatoms near step area with relatively low Au coordination numbers exist at low coverage (<1/18 ML), O adatoms adsorb at terrace areas with relatively high Au coordination numbers at medium coverage (1/18-2/9 ML); while oxygen islands form at high coverage (>2/9 ML). The theoretical predictions are in good agreement with the experimental observations in TDS spectrum. On the basis of Langmuir-Hinschelwood and Eley-Rideal mechanisms for NO oxidation, the activities of the three different oxygen species also exhibit correlation with Au coordination number. The oxygen island shows the highest oxidation activity, followed by the O adatom at terrace surface; while the O adatom near step area has the lowest oxidative performance. This work will shed light into the understanding of gold catalysis.

  8. Bactericidal activity of Ag-zeolite mediated by reactive oxygen species under aerated conditions.

    PubMed

    Inoue, Yoshihiro; Hoshino, Masanobu; Takahashi, Hiroo; Noguchi, Tomoko; Murata, Tomomi; Kanzaki, Yasushi; Hamashima, Hajime; Sasatsu, Masanori

    2002-09-30

    The bactericidal activity induced by the introduction of silver ions into zeolite was studied. Escherichia coli was used as the test microorganism. Silver ions were loaded into zeolite by the ion-exchange method. Silver-loaded zeolite was demonstrated the strong bactericidal activity. Dissolved oxygen was an essential factor for the occurrence of the bactericidal activity because the activity was observed only under aerated condition. Superoxide anions, hydrogen peroxide, hydroxyl radicals and singlet oxygen were formed. Scavengers of these each reactive oxygen species (ROS) inhibited the bactericidal activity. This means that all ROS contributed to the activity.

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

    SciTech Connect

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

    2016-01-01

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

  10. A hybrid computer program for rapidly solving flowing or static chemical kinetic problems involving many chemical species

    NASA Technical Reports Server (NTRS)

    Mclain, A. G.; Rao, C. S. R.

    1976-01-01

    A hybrid chemical kinetic computer program was assembled which provides a rapid solution to problems involving flowing or static, chemically reacting, gas mixtures. The computer program uses existing subroutines for problem setup, initialization, and preliminary calculations and incorporates a stiff ordinary differential equation solution technique. A number of check cases were recomputed with the hybrid program and the results were almost identical to those previously obtained. The computational time saving was demonstrated with a propane-oxygen-argon shock tube combustion problem involving 31 chemical species and 64 reactions. Information is presented to enable potential users to prepare an input data deck for the calculation of a problem.

  11. Spin-dependent recombination involving oxygen-vacancy complexes in silicon

    NASA Astrophysics Data System (ADS)

    Franke, David P.; Hoehne, Felix; Vlasenko, Leonid S.; Itoh, Kohei M.; Brandt, Martin S.

    2014-05-01

    Spin-dependent relaxation and recombination processes in γ-irradiated n-type Czochralski-grown silicon are studied using continuous wave (cw) and pulsed electrically detected magnetic resonance (EDMR). Two processes involving the SL1 center, the neutral excited triplet state of the oxygen-vacancy complex, are observed which can be separated by their different dynamics. One of the processes is the relaxation of the excited SL1 state to the ground state of the oxygen-vacancy complex, the other a charge transfer between 31P donors and SL1 centers forming close pairs, as indicated by electrically detected electron double resonance. For both processes, the recombination dynamics is studied with pulsed EDMR techniques. We demonstrate the feasibility of true zero-field cw and pulsed EDMR for spin-1 systems and use this to measure the lifetimes of the different spin states of SL1 also at vanishing external magnetic field.

  12. Involvement of reactive oxygen intermediates in tumor necrosis factor alpha-dependent bacteriostasis of Mycobacterium avium.

    PubMed Central

    Sarmento, A; Appelberg, R

    1996-01-01

    We studied the involvement of reactive oxygen intermediates and reactive nitrogen intermediates in the bacteriostasis of two Mycobacterium avium strains differing in virulence by resident peritoneal macrophages. We found that both the highly virulent strain (25291) and the low-virulence strain (1983) of M. avium induced superoxide production but inhibited nitrite production in vitro. This inhibition was due to the production of superoxide, a nitric oxide scavenger. The stimulation of superoxide production was two- to fivefold higher in strain 1983-infected than in strain 25291-infected resident peritoneal macrophages and was independent of contaminating T cells or NK cells. Superoxide secretion was dependent on the tumor necrosis factor (TNF) produced endogenously by the macrophages. This was also true when macrophages were isolated from infected mice. Addition of TNF to the infected resident peritoneal macrophages caused only a slight, albeit significant, increase in superoxide production by strain 25291-infected macrophages. Incubation of resident peritoneal macrophages with different scavengers of reactive oxygen intermediates showed that strain 1983 was susceptible to hydrogen peroxide produced by resident peritoneal macrophages. Strain 25291 was shown to decrease superoxide secretion inside heavily infected bone marrow-derived macrophages. This strain was also shown to be a better trigger for production of reactive oxygen intermediates than strain 1983. In summary, strain 1983 induced high levels of TNF synthesis that acted in an autocrine fashion to stimulate production of reactive oxygen intermediates by macrophages leading to growth restriction mediated by hydrogen peroxide. The highly virulent strain 25291 induced low levels of TNF synthesis, and therefore little reactive oxygen intermediate production, and could also inhibit superoxide production by the infected macrophages. PMID:8757857

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

    PubMed Central

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

    2013-01-01

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

  14. Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser.

    PubMed

    Alexsandra da Silva Neto Trajano, Larissa; da Silva, Camila Luna; de Carvalho, Simone Nunes; Cortez, Erika; Mencalha, André Luiz; de Souza da Fonseca, Adenilson; Stumbo, Ana Carolina

    2016-07-01

    Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells.

  15. Field ecology, fungal sex and food contamination involving Aspergillus species

    USDA-ARS?s Scientific Manuscript database

    Several species within the genus Aspergillus are capable of producing a myriad of toxic secondary metabolites, with aflatoxin being of most concern. These fungi happen to colonize important agricultural commodities, thereby having the potential to contaminate our food with carcinogenic aflatoxins. P...

  16. Endotoxin Disrupts Circadian Rhythms in Macrophages via Reactive Oxygen Species.

    PubMed

    Wang, Yusi; Pati, Paramita; Xu, Yiming; Chen, Feng; Stepp, David W; Huo, Yuqing; Rudic, R Daniel; Fulton, David J R

    2016-01-01

    The circadian clock is a transcriptional network that functions to regulate the expression of genes important in the anticipation of changes in cellular and organ function. Recent studies have revealed that the recognition of pathogens and subsequent initiation of inflammatory responses are strongly regulated by a macrophage-intrinsic circadian clock. We hypothesized that the circadian pattern of gene expression might be influenced by inflammatory stimuli and that loss of circadian function in immune cells can promote pro-inflammatory behavior. To investigate circadian rhythms in inflammatory cells, peritoneal macrophages were isolated from mPer2luciferase transgenic mice and circadian oscillations were studied in response to stimuli. Using Cosinor analysis, we found that LPS significantly altered the circadian period in peritoneal macrophages from mPer2luciferase mice while qPCR data suggested that the pattern of expression of the core circadian gene (Bmal1) was disrupted. Inhibition of TLR4 offered protection from the LPS-induced impairment in rhythm, suggesting a role for toll-like receptor signaling. To explore the mechanisms involved, we inhibited LPS-stimulated NO and superoxide. Inhibition of NO synthesis with L-NAME had no effect on circadian rhythms. In contrast, inhibition of superoxide with Tempol or PEG-SOD ameliorated the LPS-induced changes in circadian periodicity. In gain of function experiments, we found that overexpression of NOX5, a source of ROS, could significantly disrupt circadian function in a circadian reporter cell line (U2OS) whereas iNOS overexpression, a source of NO, was ineffective. To assess whether alteration of circadian rhythms influences macrophage function, peritoneal macrophages were isolated from Bmal1-KO and Per-TKO mice. Compared to WT macrophages, macrophages from circadian knockout mice exhibited altered balance between NO and ROS release, increased uptake of oxLDL and increased adhesion and migration. These results

  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. Photoreactivity of carboxylated single-walled carbon nanotubes in sunlight: reactive oxygen species production in water.

    PubMed

    Chen, Chia-Ying; Jafvert, Chad T

    2010-09-01

    Very limited information exists on transformation processes of carbon nanotubes in the natural aquatic environment. Because the conjugated pi-bond structure of these materials is efficient in absorbing sunlight, photochemical transformations are a potential fate process with reactivity predicted to vary with their diameter, chirality, number and type of defects, functionalization, residual metal catalyst and amorphous carbon content, and with the composition of the water, including the type and composition of materials that act to disperse them into the aqueous environment. In this study, the photochemical reactions involving colloidal dispersions of carboxylated single-walled carbon nanotubes (SWNT-COOH) in sunlight were examined. Production of reactive oxygen species (ROS) during irradiation occurs and is evidence for potential further phototransformation and may be significant in assessing their overall environmental impacts. In aerated samples exposed to sunlight or to lamps that emit light only within the solar spectrum, the probe compounds, furfuryl alcohol (FFA), tetrazolium salts (NBT2+ and XTT), and p-chlorobenzoic acid (pCBA), were used to indicate production of 1O2, O2.-, and .OH, respectively. All three ROS were produced in the presence of SWNT-COOH and molecular oxygen (3O2). 1O2 production was confirmed by observing enhanced FFA decay in deuterium oxide, attenuated decay of FFA in the presence of azide ion, and the lack of decay of FFA in deoxygenated solutions. Photogeneration of O2.- and .OH was confirmed by applying superoxide dismutase (SOD) and tert-butanol assays, respectively. In air-equilibrated suspensions, the loss of 0.2 mM FFA in 10 mg/L SWNT-COOH was approximately 85% after 74 h. Production of 1O2 was not dependent on pH from 7 to 11; however photoinduced aggregation was observed at pH 3.

  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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Increase in reactive oxygen species and activation of Akt signaling pathway in neuropathic pain.

    PubMed

    Guedes, Renata P; Araújo, Alex S R; Janner, Daiane; Belló-Klein, Adriane; Ribeiro, Maria Flávia M; Partata, Wania A

    2008-12-01

    Neuropathic pain occurs as a result of peripheral or central nervous system injury. Its pathophysiology involves mainly a central sensitization mechanism that may be correlated to many molecules acting in regions involved in pain processing, such as the spinal cord. It has been demonstrated that reactive oxygen species (ROS) and signaling molecules, such as the serine/threonine protein kinase Akt, are involved in neuropathic pain mechanisms. Thus, the aim of this study was to provide evidence of this relationship. Sciatic nerve transection (SNT) was used to induce neuropathic pain in rats. Western blot analysis of Akt and 4-hydroxy-2-nonenal (HNE)-Michael adducts, and measurement of hydrogen peroxide (H(2)O(2)) in the lumbosacral spinal cord were performed. The main findings were found seven days after SNT, when there was an increase in HNE-Michael adducts formation, total and p-Akt expression, and H(2)O(2) concentration. However, one and 15 days after SNT, H(2)O(2) concentration was raised in both sham (animals that were submitted to surgery without nerve injury) and SNT groups, showing the high sensibility of this ROS to nociceptive afferent stimuli, not only to neuropathic pain. p-Akt also increased in sham and SNT groups one day post injury, but at 3 and 7 days the increase occurred exclusively in SNT animals. Thus, there is crosstalk between intracellular signaling pathways and ROS, and these molecules can act as protective agents in acute pain situations or play a role in the development of chronic pain states.

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

    SciTech Connect

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

    2012-08-24

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

  2. Adenosine reduces reactive oxygen species and interleukin-8 production by Trichomonas vaginalis-stimulated neutrophils.

    PubMed

    Frasson, Amanda Piccoli; Menezes, Camila Braz; Goelzer, Gustavo Krumel; Gnoatto, Simone Cristina Baggio; Garcia, Solange Cristina; Tasca, Tiana

    2017-09-06

    Trichomonas vaginalis is a flagellated protozoan that affects the human urogenital tract causing 276.4 million new infections a year. The parasite elicits a vaginal mucosal infiltration of immune cells, especially neutrophils which are considered to be primarily responsible for cytological change observed at the infection site as well as the major contributor in the inflammatory response against the parasite. Extracellular nucleotides and their nucleosides are signaling compounds involved in several biological processes, including inflammation and immune responses. Once in the extracellular space, the nucleotides and nucleosides can directly activate the purinergic receptors. Herein, we investigated the involvement of purinergic signaling on the production of reactive oxygen species (ROS) and cytokines by T. vaginalis-stimulated neutrophils. Parasites were able to induce an increase in ROS and IL-8 levels while they did not promote IL-6 secretion or neutrophil elastase activity. Adenine and guanine nucleotides or nucleosides were not able to modulate ROS and cytokine production; however, when T. vaginalis-stimulated neutrophils were incubated with adenosine and adenosine deaminase inhibitor, the levels of ROS and IL-8 were significantly reduced. These immunosuppressive effects were probably a response to the higher bioavailability of adenosine found in the supernatant as result of inhibition of enzyme activity. The involvement of P1 receptors was investigated by immunofluorescence and A1 receptor was the most abundant. Our data show that the influence of purinergic signaling, specifically those effects associated with adenosine accumulation, on the modulation of production of proinflammatory mediators by T. vaginalis-stimulated neutrophils contribute to the understanding of immunological aspects of trichomoniasis.

  3. Blood biochemical and cellular changes during a decompression procedure involving eight hours of oxygen prebreathing

    NASA Technical Reports Server (NTRS)

    Jauchem, J. R.

    1989-01-01

    Chemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 8 h of oxygen prebreathing. The exposure was designed to simulate space-flight extravehicular activity (EVA) for 6 h. Several statistically significant changes in blood parameters were observed following the exposure: increases in calcium, magnesium, osmolality, low-density lipoprotein cholesterol, monocytes, and prothrombin time, and decreases in chloride, creatine phosphokinase and eosinophils. The changes, however, were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression profile used in this study is not likely to result in blood changes that would pose a threat to astronauts during EVA.

  4. Blood biochemical and cellular changes during a decompression procedure involving eight hours of oxygen prebreathing

    NASA Technical Reports Server (NTRS)

    Jauchem, J. R.

    1989-01-01

    Chemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 8 h of oxygen prebreathing. The exposure was designed to simulate space-flight extravehicular activity (EVA) for 6 h. Several statistically significant changes in blood parameters were observed following the exposure: increases in calcium, magnesium, osmolality, low-density lipoprotein cholesterol, monocytes, and prothrombin time, and decreases in chloride, creatine phosphokinase and eosinophils. The changes, however, were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression profile used in this study is not likely to result in blood changes that would pose a threat to astronauts during EVA.

  5. Ethylbenzene Dehydrogenase and Related Molybdenum Enzymes Involved in Oxygen-Independent Alkyl Chain Hydroxylation.

    PubMed

    Heider, Johann; Szaleniec, Maciej; Sünwoldt, Katharina; Boll, Matthias

    2016-01-01

    Ethylbenzene dehydrogenase initiates the anaerobic bacterial degradation of ethylbenzene and propylbenzene. Although the enzyme is currently only known from a few closely related denitrifying bacterial strains affiliated to the Rhodocyclaceae, it clearly marks a universally occurring mechanism used for attacking recalcitrant substrates in the absence of oxygen. Ethylbenzene dehydrogenase belongs to subfamily 2 of the DMSO reductase-type molybdenum enzymes together with paralogous enzymes involved in the oxygen-independent hydroxylation of p-cymene, the isoprenoid side chains of sterols and even possibly n-alkanes; the subfamily also extends to dimethylsulfide dehydrogenases, selenite, chlorate and perchlorate reductases and, most significantly, dissimilatory nitrate reductases. The biochemical, spectroscopic and structural properties of the oxygen-independent hydroxylases among these enzymes are summarized and compared. All of them consist of three subunits, contain a molybdenum-bis-molybdopterin guanine dinucleotide cofactor, five Fe-S clusters and a heme b cofactor of unusual ligation, and are localized in the periplasmic space as soluble enzymes. In the case of ethylbenzene dehydrogenase, it has been determined that the heme b cofactor has a rather high redox potential, which may also be inferred for the paralogous hydroxylases. The known structure of ethylbenzene dehydrogenase allowed the calculation of detailed models of the reaction mechanism based on the density function theory as well as QM-MM (quantum mechanics - molecular mechanics) methods, which yield predictions of mechanistic properties such as kinetic isotope effects that appeared consistent with experimental data. © 2016 S. Karger AG, Basel.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2009-05-25

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

  8. Reactive Oxygen and Nitrogen Species in Defense/Stress Responses Activated by Chitosan in Sycamore Cultured Cells

    PubMed Central

    Malerba, Massimo; Cerana, Raffaella

    2015-01-01

    Chitosan (CHT) is a non-toxic and inexpensive compound obtained by deacetylation of chitin, the main component of the exoskeleton of arthropods as well as of the cell walls of many fungi. In agriculture CHT is used to control numerous diseases on various horticultural commodities but, although different mechanisms have been proposed, the exact mode of action of CHT is still unknown. In sycamore (Acer pseudoplatanus L.) cultured cells, CHT induces a set of defense/stress responses that includes production of H2O2 and nitric oxide (NO). We investigated the possible signaling role of these reactive molecules in some CHT-induced responses by means of inhibitors of production and/or scavengers. The results show that both reactive nitrogen and oxygen species are not only a mere symptom of stress conditions but are involved in the responses induced by CHT in sycamore cells. In particular, NO appears to be involved in a cell death form induced by CHT that shows apoptotic features like DNA fragmentation, increase in caspase-3-like activity and release of cytochrome c from the mitochondrion. On the contrary, reactive oxygen species (ROS) appear involved in a cell death form induced by CHT that does not show these apoptotic features but presents increase in lipid peroxidation. PMID:25642757

  9. Reactive Oxygen Species Mediated Prostaglandin E2 Contributes to Acute Response of Epithelial Injury

    PubMed Central

    Hu, Yi-Ping; Zhang, Yi-Fan; Wang, Ying; Yu, Wei-Rong

    2017-01-01

    Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase. PMID:28280524

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

    PubMed Central

    Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2017-01-01

    Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

  11. Reactive oxygen species (ROS) in the human neocortex: role of aging and cognition.

    PubMed

    Brawek, Bianca; Löffler, Marlene; Wagner, Kathrin; Huppertz, Hans-Jürgen; Wendling, Anne-Sophie; Weyerbrock, Astrid; Jackisch, Rolf; Feuerstein, Thomas J

    2010-03-16

    Reactive oxygen species (ROS), formed during normal aerobic metabolism, are involved in signal transduction and cognitive functions, but highly increased ROS concentrations may also have detrimental effects. The aim of the present study was to investigate whether aging and cognitive functions are associated with ROS generation in human neocortex obtained from neurosurgical patients. ROS formation in mitochondria from fresh and re-thawed neocortical specimens was measured by monitoring ROS-mediated conversion of dihydrorhodamine 123 to fluorescent rhodamine 123. The validity of this technique was characterized in rat brain mitochondria. The increase in the concentration-response curve of the complex I inhibitor rotenone on ROS generation, as measured by rhodamine 123 (Rh123) fluorescence, was much more pronounced than that of rotenone on mitochondrial [(3)H]-choline uptake [which indicates changes in the mitochondrial membrane potential (DeltaPsi(M))]. Thus, mitochondrial ROS generation can be shown by Rh123 fluorescence although this fluorescence may also reflect changes in DeltaPsi(M) to some extent. ROS formation in human brain mitochondria positively correlated with the age of patients. Moreover, an age-corrected positive correlation of ROS formation with presurgical cognitive performance was observed. Our data suggest a mild increase in ROS formation with aging possibly reflecting a physiological compensation of mitochondrial function. Furthermore, higher cognitive performances in tests of executive functions may be paralleled by slightly increased ROS levels. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Cadmium induces apoptosis and genotoxicity in rainbow trout hepatocytes through generation of reactive oxygene species.

    PubMed

    Risso-de Faverney, C; Devaux, A; Lafaurie, M; Girard, J P; Bailly, B; Rahmani, R

    2001-06-01

    Cadmium poses a serious environmental threat in aquatic ecosystems but the mechanisms of its toxicity remain unclear. The purpose of this work was first to determine whether cadmium induced apoptosis in trout hepatocytes, second to determine whether or not reactive oxygen species (ROS) were involved in cadmium-induced apoptosis and genotoxicity. Hepatocytes exposed to increasing cadmium concentrations (in the range of 1-10 microM) showed a molecular hallmark of apoptosis which is the fragmentation of the nuclear DNA into oligonucleosomal-length fragments, resulting from an activation of endogenous endonucleases and recognized as a 'DNA ladder' on conventional agarose gel electrophoresis. Exposure of hepatocytes to cadmium led clearly to the DEVD-dependent protease activation, acting upstream from the endonucleases and considered as central mediators of apoptosis. DNA strand breaks in cadmium-treated trout hepatocytes was assessed using the comet assay, a rapid and sensitive single-cell gel electrophoresis technique used to detect DNA primary damage in individual cells. Simultaneous treatment of trout hepatocytes with cadmium and the nitroxide radical TEMPO used as a ROS scavenger, reduced significantly DNA fragmentation, DEVD-related protease activity and DNA strand breaks formation. These results lead to a working hypothesis that cadmium-induced apoptosis and DNA strand breaks in trout hepatocytes are partially triggered by the generation of ROS. Additional studies are required for proposing a mechanistic model of cadmium-induced apoptosis and genotoxicity in trout liver cells, in underlying the balance between DNA damage and cellular defence systems in fish.

  13. Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced senescence.

    PubMed

    Demelash, Abeba; Pfannenstiel, Lukas W; Liu, Li; Gastman, Brian R

    2017-04-25

    Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence. Mcl-1's anti-senescence activity also involves the unique ability to inhibit ROS formation by preventing the upregulation of pro-oxidants. Specifically, we found that NADPH oxidases (NOXs) are regulated by Mcl-1 and that NOX4 expression in particular is a required step for CIS induction that is blocked by Mcl-1. Lastly, we illustrate that by preventing expression of NOX4, Mcl-1 limits its availability in the mitochondria, thereby lowering the production of mitochondrial ROS during CIS. Our studies not only define the essential role of Mcl-1 in chemoresistance, but also for the first time link a key pro-survival Bcl-2 family member with the NOX protein family, both of which have significant ramifications in cancer progression.

  14. Reactive oxygen species and anti-oxidant defences in swine follicular fluids.

    PubMed

    Basini, Giuseppina; Simona, Bussolati; Santini, Sujen Eleonora; Grasselli, Francesca

    2008-01-01

    A growing body of evidence indicates that the pro-oxidant/anti-oxidant balance inside the ovarian follicle plays an important role in folliculogenesis. Therefore, the aim of the present study was to assess the redox status of follicular fluids collected from different-sized swine follicles. We quantified the most important reactive oxygen species (ROS), namely superoxide anion (O(2)(-)), hydrogen peroxide and hydroperoxides (ROOH); in addition, we examined the activity of the detoxifying enzymes superoxide dismutase, catalase (CAT) and glutathione peroxidase and the total non-enzymatic antioxidant capacity as determined by the ferric-reducing anti-oxidant power assay. Our data demonstrate that oxidative stress does not affect follicle growth because O(2)(-) levels do not change during follicle development, whereas concentrations of H2O2 and ROOH are reduced (P < 0.05). Surprisingly, all non-enzymatic and enzymatic scavengers examined in the present study, except for CAT, demonstrated reduced activity during follicle development (P < 0.05). Taken together, these results suggest that other factors could be involved in ROS detoxification during follicle development.

  15. Correlation between cell migration and reactive oxygen species under electric field stimulation

    PubMed Central

    Wu, Shang-Ying; Hou, Hsien-San; Sun, Yung-Shin; Cheng, Ji-Yen; Lo, Kai-Yin

    2015-01-01

    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

  16. Exploitation of reactive oxygen species by fungi: roles in host-fungus interaction and fungal development.

    PubMed

    Kim, Hyo Jin

    2014-11-28

    In the past, reactive oxygen species (ROS) have been considered a harmful byproduct of aerobic metabolism. However, accumulating evidence implicates redox homeostasis, which maintains appropriate ROS levels, in cell proliferation and differentiation in plants and animals. Similarly, ROS generation and signaling are instrumental in fungal development and host-fungus interaction. In fungi, NADPH oxidase, a homolog of human gp91(phox), generates superoxide and is the main source of ROS. The mechanism of activation and signaling by NADPH oxidases in fungi appears to be largely comparable to those in plants and animals. Recent studies have shown that the fungal NADPH oxidase homologs NoxA (Nox1), NoxB (Nox2), and NoxC (Nox3) have distinct functions. In particular, these studies have consistently demonstrated the impact of NoxA on the development of fungal multicellular structures. Both NoxA and NoxB (but not NoxC) are involved in host-fungus interactions, with the function of NoxA being more critical than that of NoxB.

  17. 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.

  18. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge

    PubMed Central

    Pan, Tai-Long

    2016-01-01

    Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen. PMID:27579153

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

    PubMed

    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

    2013-12-11

    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.

  20. 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

  1. 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.

  2. Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species.

    PubMed

    van den Hoven, Mabel J; Waanders, Femke; Rops, Angelique L; Kramer, Andrea B; van Goor, Harry; Berden, Jo H; Navis, Gerjan; van der Vlag, Johan

    2009-09-01

    Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides renoprotection in adriamycin nephropathy (AN), along with a decrease in overexpression of glomerular heparanase. Angiotensin II (AngII) and reactive oxygen species (ROS) are known to regulate heparanase expression in vivo. However, it is unknown whether this is also the case for aldosterone. Therefore, we further assessed the role of aldosterone, AngII and ROS in the regulation of glomerular heparanase expression. Six weeks after the induction of AN, rats were treated with vehicle (n = 8), lisinopril (75 mg/L, n = 10), spironolactone (3.3 mg/day, n = 12) or the combination of lisinopril and spironolactone (n = 14) for 12 weeks. Age-matched healthy rats served as controls (n = 6). After 18 weeks, renal heparanase and heparan sulfate (HS) expression were examined by immunofluorescence staining. In addition, the effect of aldosterone, AngII and ROS on heparanase expression in cultured podocytes was determined. Treatment with lisinopril, spironolactone or their combination significantly blunted the increased glomerular heparanase expression and restored the decreased HS expression in the GBM. Addition of aldosterone to cultured podocytes resulted in a significantly increased heparanase mRNA and protein expression, which could be inhibited by spironolactone. Heparanase mRNA and protein expression in podocytes were also significantly increased after stimulation with AngII or ROS. Our in vivo and in vitro results show that not only AngII and ROS, but also aldosterone is involved in the regulation of glomerular heparanase expression.

  3. Isoalantolactone Induces Reactive Oxygen Species Mediated Apoptosis in Pancreatic Carcinoma PANC-1 Cells

    PubMed Central

    Khan, Muhammad; Ding, Chuan; Rasul, Azhar; Yi, Fei; Li, Ting; Gao, Hongwen; Gao, Rong; Zhong, Lili; Zhang, Kun; Fang, Xuedong; Ma, Tonghui

    2012-01-01

    Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma. PMID:22532787

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

    PubMed Central

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

    2014-01-01

    The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response. PMID:21146868

  5. Reactive oxygen species contribute to lipopolysaccharide-induced teratogenesis in mice.

    PubMed

    Zhao, Lei; Chen, Yuan-Hua; Wang, Hua; Ji, Yan-Li; Ning, Huan; Wang, Su-Fang; Zhang, Cheng; Lu, Jin-Wei; Duan, Zi-Hao; Xu, De-Xiang

    2008-05-01

    Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, fetal death and growth retardation, and preterm delivery. In the present study, we showed that an ip injection with LPS daily from gestational day (gd) 8 to gd 12 resulted in the incidence of external malformations. The highest incidence of malformed fetuses was observed in fetuses from dams exposed to 20 microg/kg LPS, in which 34.9% of fetuses per litter were externally malformed. In addition, 17.4% of fetuses per litter in 30 microg/kg group and 12.5% of fetuses per litter in 10 microg/kg group were externally malformed. Importantly, external malformations were also observed in fetuses from dams exposed to only two doses of LPS (20 microg/kg, ip) on gd 8, in which 76.5% (13/17) of litters and 39.1% of fetuses per litter were affected. LPS-induced teratogenicity seemed to be associated with oxidative stress in fetal environment, measured by lipid peroxidation, nitrotyrosine residues, and glutathione (GSH) depletion in maternal liver, embryo, and placenta. alpha-Phenyl-N-t-butylnitrone (PBN, 100 mg/kg, ip), a free radical spin-trapping agent, abolished LPS-induced lipid peroxidation, nitrotyrosine residues, and GSH depletion. Consistent with its antioxidant effects, PBN decreased the incidence of external malformations. Taken together, these results suggest that reactive oxygen species might be, at least partially, involved in LPS-induced teratogenesis.

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

    PubMed

    Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2017-01-10

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

  7. Hyperthermia, dehydration, and osmotic stress: unconventional sources of exercise-induced reactive oxygen species.

    PubMed

    King, Michelle A; Clanton, Thomas L; Laitano, Orlando

    2016-01-15

    Evidence of increased reactive oxygen species (ROS) production is observed in the circulation during exercise in humans. This is exacerbated at elevated body temperatures and attenuated when normal exercise-induced body temperature elevations are suppressed. Why ROS production during exercise is temperature dependent is entirely unknown. This review covers the human exercise studies to date that provide evidence that oxidant and antioxidant changes observed in the blood during exercise are dependent on temperature and fluid balance. We then address possible mechanisms linking exercise with these variables that include shear stress, effects of hemoconcentration, and signaling pathways involving muscle osmoregulation. Since pathways of muscle osmoregulation are rarely discussed in this context, we provide a brief review of what is currently known and unknown about muscle osmoregulation and how it may be linked to oxidant production in exercise and hyperthermia. Both the circulation and the exercising muscle fibers become concentrated with osmolytes during exercise in the heat, resulting in a competition for available water across the muscle sarcolemma and other tissues. We conclude that though multiple mechanisms may be responsible for the changes in oxidant/antioxidant balance in the blood during exercise, a strong case can be made that a significant component of ROS produced during some forms of exercise reflect requirements of adapting to osmotic challenges, hyperthermia challenges, and loss of circulating fluid volume. Copyright © 2016 the American Physiological Society.

  8. DUOX2-derived reactive oxygen species are effectors of NOD2-mediated antibacterial responses.

    PubMed

    Lipinski, Simone; Till, Andreas; Sina, Christian; Arlt, Alexander; Grasberger, Helmut; Schreiber, Stefan; Rosenstiel, Philip

    2009-10-01

    Generation of microbicidal reactive oxygen species (ROS) is a pivotal protective component of the innate immune system in many eukaryotes. NOD (nucleotide oligomerisation domain containing protein)-like receptors (NLRs) have been implicated as phylogenetically ancient sensors of intracellular pathogens or endogenous danger signals. NOD2 recognizes the bacterial cell wall component muramyldipeptide leading to NFkappaB and MAPK activation via induced proximity signalling through the serine-threonine kinase RIP2. In addition to the subsequent induction of cytokines and antimicrobial peptides, NOD2 has been shown also to exert a direct antibacterial effect. Using a fluorescence-based ROS detection assay we demonstrate controlled ROS generation as an integral component of NOD2-induced signalling in epithelial cells. We demonstrate that the NAD(P)H oxidase family member DUOX2 is involved in NOD2-dependent ROS production. Coimmunoprecipitation and fluorescence microscopy were used to show that DUOX2 interacts and colocalizes with NOD2 at the plasma membrane. Moreover, simultaneous overexpression of NOD2 and DUOX2 was found to result in cooperative protection against bacterial cytoinvasion using the Listeria monocytogenes infection model. RNAi-based studies revealed that DUOX2 is required for the direct bactericidal properties of NOD2. Our results demonstrate a new role of ROS as effector molecules of protective cellular signalling in response to a defined danger signal carried out by a mammalian intracellular NLR system.

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

    PubMed

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

    2013-12-05

    In recent years, it has become well known that the production of reactive oxygen species (ROS) induced by blue-light irradiation causes adverse effects of photo-aging, such as age-related macular degeneration of the retina. Thus, orange-tinted glasses are used to protect the retina during dental treatment involving blue-light irradiation (e.g., dental resin restorations or tooth bleaching treatments). However, there are few studies examining the effects of blue-light irradiation on oral tissue. For the first time, we report that blue-light irradiation by quartz tungsten halogen lamp (QTH) or light-emitting diode (LED) decreased cell proliferation activity of human gingival fibroblasts (HGFs) in a time-dependent manner (<5 min). Additionally, in a morphological study, the cytotoxic effect was observed in the cell organelles, especially the mitochondria. Furthermore, ROS generation induced by the blue-light irradiation was detected in mitochondria of HGFs using fluorimetry. In all analyses, the cytotoxicity was significantly higher after LED irradiation compared with cytotoxicity after QTH irradiation. These results suggest that blue light irradiation, especially by LED light sources used in dental aesthetic treatment, might have adverse effects on human gingival tissue. Hence, this necessitates the development of new dental aesthetic treatment methods and/or techniques to protect HGFs from blue light irradiation during dental therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies

    PubMed Central

    Muntean, Danina M.; Sturza, Adrian; Dănilă, Maria D.; Borza, Claudia; Duicu, Oana M.; Mornoș, Cristian

    2016-01-01

    Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed. PMID:27200148

  11. Reactive oxygen species modulate Zn(2+)-induced apoptosis in cancer cells.

    PubMed

    Provinciali, Mauro; Donnini, Alessia; Argentati, Katy; Di Stasio, Grazia; Bartozzi, Beatrice; Bernardini, Giovanni

    2002-03-01

    Some recent evidence has suggested a protective role of zinc against cancer. The mechanism by which zinc exerts this action has not been defined and, in particular, it has not been clarified whether zinc may directly act on cancer cells and the molecular mechanisms involved in this effect. In this study, we examined the in vitro effect of zinc on the apoptosis of mouse TS/A mammary adenocarcinoma cells, studying the zinc-dependent modulation of the intracellular levels of reactive oxygen species (ROS) and of p53 and Fas/Fas ligand pathways. We showed that zinc concentrations ranging from 33.7 to 75 muM Zn(2+) induced apoptosis in mammary cancer cells. The apoptosis was associated with an increased production of intracellular ROS, and of p53 and Fas/Fas ligand mRNA and protein. Zn(2+) induced a faint metallothionein response in TS/A cells in comparison with mouse lymphocytes. The 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. The data demonstrate that zinc exerts a direct action on mammary cancer cells inducing ROS-mediated apoptosis and that the effect may be mediated by the ROS-dependent induction of p53 and Fas/Fas ligand.

  12. Mitochondrial metabolism, reactive oxygen species, and macrophage function-fishing for insights.

    PubMed

    Hall, Christopher J; Sanderson, Leslie E; Crosier, Kathryn E; Crosier, Philip S

    2014-11-01

    Metabolism and defense mechanisms that protect against pathogens are two fundamental requirements for the survival of multicellular organisms. Research into metabolic disease has revealed these core mechanisms are highly co-dependent. This emerging field of research, termed immunometabolism, focuses on understanding how metabolism influences immunological processes and vice versa. It is now accepted that obesity influences the immune system and that obesity-driven inflammation contributes to many diseases including type 2 diabetes, cardiovascular disease and Alzheimer's disease. The immune response requires the reallocation of nutrients within immune cells to different metabolic pathways to satisfy energy demands and the production of necessary macromolecules. One aspect of immunometabolic research is understanding how these metabolic changes help regulate specific immune cell functions. It is hoped that further understanding of the pathways involved in managing this immunological-metabolic interface will reveal new ways to treat metabolic disease. Given their growing status as principle drivers of obesity-associated inflammation, monocytes/macrophages have received much attention when studying the consequences of inflammation within adipose tissue. Less is known regarding how metabolic changes within macrophages (metabolic reprogramming) influence their immune cell function. In this review, we focus on our current understanding of how monocytes/macrophages alter their intracellular metabolism during the immune response and how these changes dictate specific effector functions. In particular, the immunomodulatory functions of mitochondrial metabolism and mitochondrial reactive oxygen species. We also highlight how the attributes of the zebrafish model system can be exploited to reveal new mechanistic insights into immunometabolic processes.

  13. Increased reactive oxygen species production during reductive stress: The roles of mitochondrial glutathione and thioredoxin reductases.

    PubMed

    Korge, Paavo; Calmettes, Guillaume; Weiss, James N

    2015-01-01

    Both extremes of redox balance are known to cause cardiac injury, with mounting evidence revealing that the injury induced by both oxidative and reductive stress is oxidative in nature. During reductive stress, when electron acceptors are expected to be mostly reduced, some redox proteins can donate electrons to O2 instead, which increases reactive oxygen species (ROS) production. However, the high level of reducing equivalents also concomitantly enhances ROS scavenging systems involving redox couples such as NADPH/NADP+ and GSH/GSSG. Here our objective was to explore how reductive stress paradoxically increases net mitochondrial ROS production despite the concomitant enhancement of ROS scavenging systems. Using recombinant enzymes and isolated permeabilized cardiac mitochondria, we show that two normally antioxidant matrix NADPH reductases, glutathione reductase and thioredoxin reductase, generate H2O2 by leaking electrons from their reduced flavoprotein to O2 when electron flow is impaired by inhibitors or because of limited availability of their natural electron acceptors, GSSG and oxidized thioredoxin. The spillover of H2O2 under these conditions depends on H2O2 reduction by peroxiredoxin activity, which may regulate redox signaling in response to endogenous or exogenous factors. These findings may explain how ROS production during reductive stress overwhelms ROS scavenging capability, generating the net mitochondrial ROS spillover causing oxidative injury. These enzymes could potentially be targeted to increase cancer cell death or modulate H2O2-induced redox signaling to protect the heart against ischemia/reperfusion damage.

  14. Removal of reactive oxygen species induced 3’-blocked ends by XPF-ERCC1

    PubMed Central

    Fisher, Laura A.; Samson, Laura; Bessho, Tadayoshi

    2011-01-01

    XPF-ERCC1 is a structure-specific endonuclease that is essential for nucleotide excision repair and DNA interstrand cross-link repair in mammalian cells. The yeast counterpart of XPF-ERCC1, Rad1-Rad10, plays multiple roles in DNA repair. Rad1-Rad10 is implicated to be involved in the repair of oxidative DNA damage. To explore the role(s) of XPF-ERCC1 in the repair of DNA damage induced by reactive oxygen species (ROS), cellular sensitivity of the XPF-deficient Chinese hamster ovary cell-line UV41 to ROS was investigated. The XPF-deficient UV41 showed sensitivity to hydrogen peroxide, bleomycin and paraquat. Furthermore, XPF-ERCC1 showed an ability to remove 3’-blocked ends such as 3’-phosphoglycolate from the 3’-end of DNA in vitro. These data suggest that XPF-ERCC1 plays a role in the repair of ROS-induced DNA damage by trimming 3’-blocked ends. The accumulation of various types of DNA damage, including ROS-induced DNA damage due to defects in multiple XPF-ERCC1-mediated DNA repair pathways, could contribute to the accelerated aging phenotypes observed in an XPF-ERCC1 deficient patient. PMID:22007867

  15. 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.

  16. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function

    PubMed Central

    Burger, Dylan; Turner, Maddison; Munkonda, Mercedes N.; Touyz, Rhian M.

    2016-01-01

    Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs) and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS) and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2∙−) generation, and nitric oxide (NO) production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47phox, p67phox, and p22phox and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2∙− production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation. PMID:27313830

  17. Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in colon cancer cells.

    PubMed

    Lim, Ji-Hong; Lee, Yoon-Mi; Park, Sa Ra; Kim, Da Hye; Lim, Beong Ou

    2014-08-01

    Few studies have been performed on the anticancer activity of hispidin, a phenolic compound produced from the medicinal mushroom Phellinus linteus. Herein, we studied hispidin-induced apoptosis, which is associated with the generation of reactive oxygen species (ROS) in colon cancer cells. Hispidin was found to reduce cell viability both in mouse and human colon cancer cells. Apoptotic cell morphological changes were observed by microscopy, and apoptosis was assessed in hispidin-treated cells using a biochemical method. The results showed accumulation of the sub-G1 cell population and increase in early apoptosis in a dose-dependent manner. In addition, hispidin induced apoptosis through up-regulation of both intrinsic and extrinsic apoptotic pathways. Although the molecular mechanism underlying hispidin-induced apoptosis is known to involve the generation of ROS, however hispidin did not show any apoptosis in the pre-treatment with a ROS scavenger, N-acetyl-L-cysteine. In conclusion, hispidin induces both intrinsic and extrinsic apoptotic pathways mediated by ROS in colon cancer cells, thereby suggesting that hispidin could be a promising new anticancer agent. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Catalase eliminates reactive oxygen species and influences the intestinal microbiota of shrimp.

    PubMed

    Yang, Hui-Ting; Yang, Ming-Chong; Sun, Jie-Jie; Guo, Fang; Lan, Jiang-Feng; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

    2015-11-01

    Intestinal innate immune response is an important defense mechanism of animals and humans against external pathogens. The mechanism of microbiota homeostasis in host intestines has been well studied in mammals and Drosophila. The reactive oxygen species (ROS) and antimicrobial peptides have been reported to play important roles in homeostasis. However, how to maintain the microbiota homeostasis in crustacean intestine needs to be elucidated. In this study, we identified a novel catalase (MjCAT) involved in ROS elimination in kuruma shrimp, Marsupenaeus japonicus. MjCAT mRNA was widely distributed in hemocytes, heart, hepatopancreas, gills, stomach, and intestine. After the shrimp were challenged with pathogenic bacteria via oral infection, the expression level of MjCAT was upregulated, and the enzyme activity was increased in the intestine. ROS level was also increased in the intestine at early time after oral infection and recovered rapidly. When MjCAT was knocked down by RNA interference (RNAi), high ROS level maintained longer time, and the number of bacteria number was declined in the shrimp intestinal lumen than those in the control group, but the survival rate of the MjCAT-RNAi shrimp was declined. Further study demonstrated that the intestinal villi protruded from epithelial lining of the intestinal wall were damaged by the high ROS level in MjCAT-knockdown shrimp. These results suggested that MjCAT participated in the intestinal host-microbe homeostasis by regulating ROS level.

  19. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge.

    PubMed

    Hung, Yu-Chiang; Pan, Tai-Long; Hu, Wen-Long

    2016-01-01

    Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

  20. Reactive oxygen species are important mediators of taurine release from skeletal muscle cells.

    PubMed

    Ørtenblad, Niels; Young, Jette Feveile; Oksbjerg, Niels; Nielsen, Jacob Holm; Lambert, Ian Henry

    2003-06-01

    The present study illustrates elements of the signal cascades involved in the activation of taurine efflux pathways in myotubes derived from skeletal muscle cells. Exposing primary skeletal muscle cells, loaded with (14)C-taurine, to 1) hypotonic media, 2) the phospholipase A(2) (PLA(2)) activator melittin, 3) anoxia, or 4) lysophosphatidyl choline (LPC) causes an increase in (14)C-taurine release and a concomitant production of reactive oxygen species (ROS). The antioxidants butulated hydroxy toluene and vitamin E inhibit the taurine efflux after cell swelling, anoxia, and addition of LPC. The muscle cells possess two separate taurine efflux pathways, i.e., a swelling- and melittin-induced pathway that requires 5-lipoxygenase activity for activation and a LPC-induced pathway. The two pathways are distinguished by their opposing sensitivity toward the anion channel blocker DIDS and cholesterol. These data provide evidence for PLA(2) products and ROS as key mediators of the signal cascade leading to taurine efflux in muscle.

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

    PubMed

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

    2012-12-10

    Cell cycle regulation is performed by cyclins and cyclin dependent kinases (CDKs). Recently, it has become clear that reactive oxygen species (ROS) influence the presence and activity of these enzymes and thereby control cell cycle progression. In this review, we first describe the discovery of enzymes specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery led to the recognition of ROS as essential players in many cellular processes, including cell cycle progression. ROS influence cell cycle progression in a context-dependent manner via phosphorylation and ubiquitination of CDKs and cell cycle regulatory molecules. We show that ROS often regulate ubiquitination via intermediate phosphorylation and that phosphorylation is thus the major regulatory mechanism influenced by ROS. In addition, ROS have recently been shown to be able to activate growth factor receptors. We will illustrate the diverse roles of ROS as mediators in cell cycle regulation by incorporating phosphorylation, ubiquitination and receptor activation in a model of cell cycle regulation involving EGF-receptor activation. We conclude that ROS can no longer be ignored when studying cell cycle progression. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Survival Signaling by C-RAF: Mitochondrial Reactive Oxygen Species and Ca2+ Are Critical Targets▿

    PubMed Central

    Kuznetsov, Andrey V.; Smigelskaite, Julija; Doblander, Christine; Janakiraman, Manickam; Hermann, Martin; Wurm, Martin; Scheidl, Stefan F.; Sucher, Robert; Deutschmann, Andrea; Troppmair, Jakob

    2008-01-01

    Survival signaling by RAF occurs through largely unknown mechanisms. Here we provide evidence for the first time that RAF controls cell survival by maintaining permissive levels of mitochondrial reactive oxygen species (ROS) and Ca2+. Interleukin-3 (IL-3) withdrawal from 32D cells resulted in ROS production, which was suppressed by activated C-RAF. Oncogenic C-RAF decreased the percentage of apoptotic cells following treatment with staurosporine or the oxidative stress-inducing agent tert-butyl hydroperoxide. However, it was also the case that in parental 32D cells growing in the presence of IL-3, inhibition of RAF signaling resulted in elevated mitochondrial ROS and Ca2+ levels. Cell death is preceded by a ROS-dependent increase in mitochondrial Ca2+, which was absent from cells expressing transforming C-RAF. Prevention of mitochondrial Ca2+ overload after IL-3 deprivation increased cell viability. MEK was essential for the mitochondrial effects of RAF. In summary, our data show that survival control by C-RAF involves controlling ROS production, which otherwise perturbs mitochondrial Ca2+ homeostasis. PMID:18212057

  3. Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice.

    PubMed

    Kevin, Leo G; Novalija, Enis; Stowe, David F

    2005-11-01

    Reactive oxygen species (ROS) are central to cardiac ischemic and reperfusion injury. They contribute to myocardial stunning, infarction and apoptosis, and possibly to the genesis of arrhythmias. Multiple laboratory studies and clinical trials have evaluated the use of scavengers of ROS to protect the heart from the effects of ischemia and reperfusion. Generally, studies in animal models have shown such effects. Clinical trials have also shown protective effects of scavengers, but whether this protection confers meaningful clinical benefits is uncertain. Several IV anesthetic drugs act as ROS scavengers. In contrast, volatile anesthetics have recently been demonstrated to generate ROS in the heart, most likely because of inhibitory effects on cardiac mitochondria. ROS are involved in the signaling cascade for cardioprotection induced by brief exposure to a volatile anesthetic (termed "anesthetic preconditioning"). ROS, therefore, although injurious in large quantities, can have a paradoxical protective effect within the heart. In this review we provide background information on ROS formation and elimination relevant to anesthetic and adjuvant drugs with particular reference to the heart. The sources of ROS, the means by which they induce cardiac injury or activate protective signaling pathways, the results of clinical studies evaluating ROS scavengers, and the effects of anesthetic drugs on ROS are each discussed.

  4. Differential production of reactive oxygen species in distinct brain regions of hypoglycemic mice.

    PubMed

    Amador-Alvarado, Leticia; Montiel, Teresa; Massieu, Lourdes

    2014-09-01

    Hypoglycemia is a serious complication of insulin therapy in patients suffering from type 1 Diabetes Mellitus. Severe hypoglycemia leading to coma (isoelectricity) induces massive neuronal death in vulnerable brain regions such as the hippocampus, the striatum and the cerebral cortex. It has been suggested that the production of reactive oxygen species (ROS) and oxidative stress is involved in hypoglycemic brain damage, and that ROS generation is stimulated by glucose reintroduction (GR) after the hypoglycemic coma. However, the distribution of ROS in discrete brain regions has not been studied in detail. Using the oxidation sensitive marker dihydroethidium (DHE) we have investigated the distribution of ROS in different regions of the mouse brain during prolonged severe hypoglycemia without isoelectricity, as well as the effect of GR on ROS levels. Results show that ROS generation increases in the hippocampus, the cerebral cortex and the striatum after prolonged severe hypoglycemia before the coma. The hippocampus showed the largest increases in ROS levels. GR further stimulated ROS production in the hippocampus and the striatum while in the cerebral cortex, only the somatosensory and parietal areas were significantly affected by GR. Results suggest that ROS are differentially produced during the hypoglycemic insult and that a different response to GR is present among distinct brain regions.

  5. 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.

  6. 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.

  7. Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

    PubMed Central

    Fakhruddin, Selim; Alanazi, Wael

    2017-01-01

    Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. PMID:28164134

  8. Imidazoles Induce Reactive Oxygen Species in Mycobacterium tuberculosis Which Is Not Associated with Cell Death

    PubMed Central

    2017-01-01

    Azoles are a class of antimicrobial drugs used clinically to treat yeast and fungal infections. Against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome P450 Cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. Azoles have antibacterial activity, including against mycobacteria, but the basis for this activity is not well-understood. We demonstrated that imidazoles are bactericidal to Mycobacterium tuberculosis. A marked increase in reactive oxygen species (ROS) was observed within imidazole-treated M. tuberculosis. The generation of ROS did not appear to be related to the mechanism of killing of imidazoles, as the addition of antioxidants or altered expression of detoxifying enzymes had no effect on growth. We examined the metabolic changes induced by econazole treatment in both wild-type and econazole-resistant mutant strains of M. tuberculosis. Econazole treatment induced changes in carbohydrates, amino acids, and energy metabolism in both strains. Notably, the untreated mutant strain had a metabolic profile similar to the wild-type drug-treated cells, suggesting that adaptation to similar stresses may play a role in econazole resistance. PMID:28180188

  9. Significant levels of extracellular reactive oxygen species produced by brown rot basidiomycetes on cellulose

    Treesearch

    Roni Cohen; Kenneth A. Jensen; Carl J. Houtman; Kenneth E. Hammel

    2002-01-01

    It is often proposed that brown rot basidiomycetes use extracellular reactive oxygen species (ROS) to accomplish the initial depolymerization of cellulose in wood, but little evidence has been presented to show that the fungi produce these oxidants in physiologically relevant quantities. We used [14C]phenethyl polyacrylate as a radical trap to estimate extracellular...

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. [Reactive oxygen species and 3,4-dihydroxyphenylacetaldehyde in pathogenesis of Parkinson disease].

    PubMed

    Rybakowska, Iwona; Szreder, Grzegorz; Kaletha, Krystian; Barwina, Małgorzata; Waldman, Wojciech; Sein Anand, Jacek

    2011-01-01

    Reactive oxygen species, which plays a role in pathogenesis of many neurodegenerative diseases, seems to be important also in pathogenesis of the Parkinson's disease. Experiments performed recently, revealed in the cerebrum of patients suffering from this disease (induced by the oxidative stress) elevated levels of 3,4-dihydroxyphenylacetaldehyde (DOPAL)--a strong endogenous neurotoxin to dopamine neurons.

  13. Reactive oxygen species in photochemistry of the red fluorescent protein "Killer Red".

    PubMed

    Vegh, Russell B; Solntsev, Kyril M; Kuimova, Marina K; Cho, Soohee; Liang, Yue; Loo, Bernard L W; Tolbert, Laren M; Bommarius, Andreas S

    2011-05-07

    The fluorescent protein aptly named "Killer Red" (KRed) is capable of killing transfected cells and inactivating fused proteins upon exposure to visible light in the presence of oxygen. We have investigated the source of the bioactive species through a variety of photophysical and photochemical techniques. Our results indicate a Type I (electron transfer mediated) photosensitizing mechanism.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  16. Reactive Oxygen Species-Inducible ECF σ Factors of Bradyrhizobium japonicum

    PubMed Central

    Masloboeva, Nadezda; Reutimann, Luzia; Stiefel, Philipp; Follador, Rainer; Leimer, Nadja; Hennecke, Hauke; Mesa, Socorro; Fischer, Hans-Martin

    2012-01-01

    Extracytoplasmic function (ECF) σ factors control the transcription of genes involved in different cellular functions, such as stress responses, metal homeostasis, virulence-related traits, and cell envelope structure. The genome of Bradyrhizobium japonicum, the nitrogen-fixing soybean endosymbiont, encodes 17 putative ECF σ factors belonging to nine different ECF σ factor families. The genes for two of them, ecfQ (bll1028) and ecfF (blr3038), are highly induced in response to the reactive oxygen species hydrogen peroxide (H2O2) and singlet oxygen (1O2). The ecfF gene is followed by the predicted anti-σ factor gene osrA (blr3039). Mutants lacking EcfQ, EcfF plus OsrA, OsrA alone, or both σ factors plus OsrA were phenotypically characterized. While the symbiotic properties of all mutants were indistinguishable from the wild type, they showed increased sensitivity to singlet oxygen under free-living conditions. Possible target genes of EcfQ and EcfF were determined by microarray analyses, and candidate genes were compared with the H2O2-responsive regulon. These experiments disclosed that the two σ factors control rather small and, for the most part, distinct sets of genes, with about half of the genes representing 13% of the members of H2O2-responsive regulon. To get more insight into transcriptional regulation of both σ factors, the 5′ ends of ecfQ and ecfF mRNA were determined. The presence of conserved sequence motifs in the promoter region of ecfQ and genes encoding EcfQ-like σ factors in related α-proteobacteria suggests regulation via a yet unknown transcription factor. By contrast, we have evidence that ecfF is autoregulated by transcription from an EcfF-dependent consensus promoter, and its product is negatively regulated via protein-protein interaction with OsrA. Conserved cysteine residues 129 and 179 of OsrA are required for normal function of OsrA. Cysteine 179 is essential for release of EcfF from an EcfF-OsrA complex upon H2O2 stress while

  17. Diffusion pathways of oxygen species in the phototoxic fluorescent protein KillerRed.

    PubMed

    Roy, Arijit; Carpentier, Philippe; Bourgeois, Dominique; Field, Martin

    2010-10-28

    The fluorescent protein KillerRed generates reactive oxygen species through the CALI effect. This property paves the way for the design of genetically encoded photosensitizers for use in cell killing and cancer photodynamic therapy. In this article, we have investigated the diffusion pathways of di-oxygen and the superoxide radical in KillerRed, using molecular dynamics simulations. Our results suggest that, by comparison to the Ser-65-Thr mutant of GFP, diffusion of molecular oxygen (and singlet oxygen) is greatly facilitated in KillerRed, mostly due to the presence of a unique water-filled channel. In contrast, due to their negative charge, superoxide radical ions putatively produced inside the chromophore pocket are unable to escape the protein. These results are consistent with the hypothesis that superoxide generation, if it occurs, proceeds via light-induced photoreduction of the chromophore followed by long-range electron transfer, a mechanism in which the long hydrogen bond network through the channel could play a key role. Alternatively, the facilitated diffusion of di-oxygen through the channel suggests that singlet di-oxygen could be the principal cause of specific CALI of fused proteins. The entry of di-oxygen through the channel probably also accounts for the high susceptibility of KillerRed to photobleaching.

  18. Production of Reactive Oxygen Species by Photosystem II as a Response to Light and Temperature Stress

    PubMed Central

    Pospíšil, Pavel

    2016-01-01

    The effect of various abiotic stresses on photosynthetic apparatus is inevitably associated with formation of harmful reactive oxygen species (ROS). In this review, recent progress on ROS production by photosystem II (PSII) as a response to high light and high temperature is overviewed. Under high light, ROS production is unavoidably associated with energy transfer and electron transport in PSII. Singlet oxygen is produced by the energy transfer form triplet chlorophyll to molecular oxygen formed by the intersystem crossing from singlet chlorophyll in the PSII antennae complex or the recombination of the charge separated radical pair in the PSII reaction center. Apart to triplet chlorophyll, triplet carbonyl formed by lipid peroxidation transfers energy to molecular oxygen forming singlet oxygen. On the PSII electron acceptor side, electron leakage to molecular oxygen forms superoxide anion radical which dismutes to hydrogen peroxide which is reduced by the non-heme iron to hydroxyl radical. On the PSII electron donor side, incomplete water oxidation forms hydrogen peroxide which is reduced by manganese to hydroxyl radical. Under high temperature, dark production of singlet oxygen results from lipid peroxidation initiated by lipoxygenase, whereas incomplete water oxidation forms hydrogen peroxide which is reduced by manganese to hydroxyl radical. The understanding of molecular basis for ROS production by PSII provides new insight into how plants survive under adverse environmental conditions. PMID:28082998

  19. Involvement of Activated Oxygen in Nitrate-Induced Senescence of Pea Root Nodules.

    PubMed Central

    Escuredo, P. R.; Minchin, F. R.; Gogorcena, Y.; Iturbe-Ormaetxe, I.; Klucas, R. V.; Becana, M.

    1996-01-01

    The effect of short-term nitrate application (10 mM, 0-4 d) on nitrogenase (N2ase) activity, antioxidant defenses, and related parameters was investigated in pea (Pisum sativum L. cv Frilene) nodules. The response of nodules to nitrate comprised two stages. In the first stage (0-2 d), there were major decreases in N2ase activity and N2ase-linked respiration and concomitant increases in carbon cost of N2ase and oxygen diffusion resistance of nodules. There was no apparent oxidative damage, and the decline in N2ase activity was, to a certain extent, reversible. The second stage (>2 d) was typical of a senescent, essentially irreversible process. It was characterized by moderate increases in oxidized proteins and catalytic Fe and by major decreases in antioxidant enzymes and metabolites. The restriction in oxygen supply to bacteroids may explain the initial decline in N2ase activity. The decrease in antioxidant protection is not involved in this process and is not specifically caused by nitrate, since it also occurs with drought stress. However, comparison of nitrate- and drought-induced senescence shows an important difference: there is no lipid degradation or lipid peroxide accumulation with nitrate, indicating that lipid peroxidation is not necessarily involved in nodule senescence. PMID:12226252

  20. Spreading the news: subcellular and organellar reactive oxygen species production and signalling.

    PubMed

    Mignolet-Spruyt, Lorin; Xu, Enjun; Idänheimo, Niina; Hoeberichts, Frank A; Mühlenbock, Per; Brosché, Mikael; Van Breusegem, Frank; Kangasjärvi, Jaakko

    2016-06-01

    As plants are sessile organisms that have to attune their physiology and morphology continuously to varying environmental challenges in order to survive and reproduce, they have evolved complex and integrated environment-cell, cell-cell, and cell-organelle signalling circuits that regulate and trigger the required adjustments (such as alteration of gene expression). Although reactive oxygen species (ROS) are essential components of this network, their pathways are not yet completely unravelled. In addition to the intrinsic chemical properties that define the array of interaction partners, mobility, and stability, ROS signalling specificity is obtained via the spatiotemporal control of production and scavenging at different organellar and subcellular locations (e.g. chloroplasts, mitochondria, peroxisomes, and apoplast). Furthermore, these cellular compartments may crosstalk to relay and further fine-tune the ROS message. Hence, plant cells might locally and systemically react upon environmental or developmental challenges by generating spatiotemporally controlled dosages of certain ROS types, each with specific chemical properties and interaction targets, that are influenced by interorganellar communication and by the subcellular location and distribution of the involved organelles, to trigger the suitable acclimation responses in association with other well-established cellular signalling components (e.g. reactive nitrogen species, phytohormones, and calcium ions). Further characterization of this comprehensive ROS signalling matrix may result in the identification of new targets and key regulators of ROS signalling, which might be excellent candidates for engineering or breeding stress-tolerant plants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Identifying the role of reactive oxygen species (ROSs) in Fusarium solani spores inactivation.

    PubMed

    Du, Yilin; Xiong, Houfeng; Dong, Shuangshi; Zhang, Jun; Ma, Dongmei; Zhou, Dandan

    2016-12-01

    The inactivation mechanism of photocatalytic disinfectants on bacteria is well known. In contrast, the potential inactivation of fungal spores by visible-light induced photocatalysis has been recognized, but the inactivation mechanism is poorly understood. We hypothesize that photocatalytically generated reactive oxygen species (ROSs) are directly involved in this mechanism. To test this hypothesis, we identified the roles of ROSs in the inactivation of Fusarium solani spores. As the photocatalysts, we doped TiO2 with 3 typical dopants, forming Ag/TiO2, N/TiO2 and Er(3+):YAlO3/TiO2. The Ag/TiO2 photocatalysis was dominated by H2O2, with the longest lifetime among the investigated ROSs. Ag/TiO2 photocatalysis yielded almost 100 % inactivation efficiency and preserved the cell-wall shape of the spores, thus minimizing the biomolecule leakage. Er(3+):YAlO3/TiO2 was dominated by h(+) ROSs, yielding an inactivation efficiency of 91 %; however, the severe leakage released large numbers of molecular bio-products. Severe damage to the cell walls by the h(+) species was confirmed in micrograph observations. Subsequent to cell wall breakage, the Er(3+):YAlO3/TiO2 nanoparticles entered the spore cells and directly oxidized the intracellular material. The N/TiO2 photocatalysis, with •O2(-) dominated ROSs, delivered intermediate performance. In conclusion, photocatalysts that generate H2O2-dominated ROSs are most preferred for spore inactivation.

  2. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes.

    PubMed

    Al-Gubory, Kaïs H; Fowler, Paul A; Garrel, Catherine

    2010-10-01

    Reactive oxygen species (ROS) are generated as by-products of aerobic respiration and metabolism. Mammalian cells have evolved a variety of enzymatic mechanisms to control ROS production, one of the central elements in signal transduction pathways involved in cell proliferation, differentiation and apoptosis. Antioxidants also ensure defenses against ROS-induced damage to lipids, proteins and DNA. ROS and antioxidants have been implicated in the regulation of reproductive processes in both animal and human, such as cyclic luteal and endometrial changes, follicular development, ovulation, fertilization, embryogenesis, embryonic implantation, and placental differentiation and growth. In contrast, imbalances between ROS production and antioxidant systems induce oxidative stress that negatively impacts reproductive processes. High levels of ROS during embryonic, fetal and placental development are a feature of pregnancy. Consequently, oxidative stress has emerged as a likely promoter of several pregnancy-related disorders, such as spontaneous abortions, embryopathies, preeclampsia, fetal growth restriction, preterm labor and low birth weight. Nutritional and environmental factors may contribute to such adverse pregnancy outcomes and increase the susceptibility of offspring to disease. This occurs, at least in part, via impairment of the antioxidant defense systems and enhancement of ROS generation which alters cellular signalling and/or damage cellular macromolecules. The links between oxidative stress, the female reproductive system and development of adverse pregnancy outcomes, constitute important issues in human and animal reproductive medicine. This review summarizes the role of ROS in female reproductive processes and the state of knowledge on the association between ROS, oxidative stress, antioxidants and pregnancy outcomes in different mammalian species.

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2009-07-31

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

  5. Elevated Cytosolic Na+ Increases Mitochondrial Formation of Reactive Oxygen Species in Failing Cardiac Myocytes

    PubMed Central

    Kohlhaas, Michael; Liu, Ting; Knopp, Andreas; Zeller, Tanja; Ong, Mei Fang; Böhm, Michael; O'Rourke, Brian; Maack, Christoph

    2010-01-01

    Background —Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart failure, elevated cytosolic Na+ ([Na+]i) reduces mitochondrial Ca2+ ([Ca2+]m) by accelerating Ca2+ efflux via the mitochondrial Na+/Ca2+ exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by [Ca2+]m, we speculated that in failing myocytes, elevated [Na+]i promotes oxidative stress. Methods and Results —We used a patch-clamp–based approach to simultaneously monitor cytosolic and mitochondrial Ca2+ and, alternatively, mitochondrial H2O2 together with NAD(P)H in guinea pig cardiac myocytes. Cells were depolarized in a voltage-clamp mode (3 Hz), and a transition of workload was induced by β-adrenergic stimulation. During this transition, NAD(P)H initially oxidized but recovered when [Ca2+]m increased. The transient oxidation of NAD(P)H was closely associated with an increase in mitochondrial H2O2 formation. This reactive oxygen species formation was potentiated when mitochondrial Ca2+ uptake was blocked (by Ru360) or Ca2+ efflux was accelerated (by elevation of [Na+]i). In failing myocytes, H2O2 formation was increased, which was prevented by reducing mitochondrial Ca2+ efflux via the mitochondrial Na+/Ca2+ exchanger. Conclusions —Besides matching energy supply and demand, mitochondrial Ca2+ uptake critically regulates mitochondrial reactive oxygen species production. In heart failure, elevated [Na+]i promotes reactive oxygen species formation by reducing mitochondrial Ca2+ uptake. This novel mechanism, by which defects in ion homeostasis induce oxidative stress, represents a potential drug target to reduce reactive oxygen species production in the failing heart. PMID:20351235

  6. Increased reactive oxygen species production and p47phox phosphorylation in neutrophils from myeloproliferative disorders patients with JAK2 (V617F) mutation

    PubMed Central

    Hurtado-Nedelec, Margarita; Csillag-Grange, Marie-José; Boussetta, Tarek; Belambri, Sahra Amel; Fay, Michèle; Cassinat, Bruno; Gougerot-Pocidalo, Marie-Anne; Dang, Pham My-Chan; El-Benna, Jamel

    2013-01-01

    Myeloproliferative disorders are associated with increased risk of thrombosis and vascular complications. The pathogenesis of these complications is not completely known. Reactive oxygen species produced by the neutrophil NADPH oxidase could have a role in this process. The aim of this study was to evaluate reactive oxygen species production by neutrophils of myeloproliferative disorder patients. Patients with or without the JAK2 V617F mutation were characterized. Reactive oxygen species production was assessed by chemiluminescence, and phosphorylation of the NADPH oxidase subunit p47phox was analyzed by Western blots. In a comparison of controls and myeloproliferative disorder patients without the JAK2 V617F mutation, reactive oxygen species production by neutrophils from patients with the JAK2 V617F mutation was dramatically increased in non-stimulated and in stimulated conditions. This increase was associated with increased phosphorylation of the p47phox on Ser345 and of the uspstream kinase ERK1/2. In neutrophils from healthy donors, JAK2 can be activated by GM-CSF. GM-CSF-induced p47phox phosphorylation and priming of reactive oxygen species production are inhibited by the selective JAK2 inhibitors AG490 and lestaurtinib (CEP-701), supporting a role for JAK2 in the upregulation of NADPH oxidase activation. These findings show an increase in reactive oxygen