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Sample records for activated oxygen species

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

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

    PubMed Central

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

    1998-01-01

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

  7. 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.

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

    PubMed Central

    Molloy, Jennifer C.; Sinkins, Steven P.

    2015-01-01

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

  9. Role of activated oxygen species on the mutagenicity of benzo[a]pyrene.

    PubMed

    Wei, C E; Allen, K; Misra, H P

    1989-06-01

    Different scavengers of active oxygen species (superoxide dismutase, catalase, mannitol and dimethylfuran) were tested in the Ames Salmonella assay to determine the role of the reactive oxygen species in the benzo[a]pyrene (B[a]P) mutagenesis process. Exogenously added superoxide dismutase or catalase at 10-100 micrograms ml-1 top agar, or 3-12 mM mannitol showed no effect on B[a]P mutagenicity in the presence of S9 mix. However, dimethylfuran (DMF), a singlet oxygen scavenger, inhibited in a dose-related manner the mutagenic response of B[a]P in the presence of the microsomal fraction. DMF at 3 and 6 mM inhibited the number of revertants by 69 and 93% for strain TA 100, and 76 and 78% for TA98, respectively. DMF at these levels was neither toxic nor mutagenic to the bacteria. The result indicates that singlet oxygen may play an important role in promoting B[a]P mutagenicity.

  10. Function of reactive oxygen species during animal development: passive or active?

    PubMed

    Covarrubias, Luis; Hernández-García, David; Schnabel, Denhí; Salas-Vidal, Enrique; Castro-Obregón, Susana

    2008-08-01

    Oxidative stress is considered causal of aging and pathological cell death, however, very little is known about its function in the natural processes that support the formation of an organism. It is generally thought that cells must continuously protect themselves from the possible damage caused by reactive oxygen species (ROS) (passive ROS function). However, presently, ROS are recognized as physiologically relevant molecules that mediate cell responses to a variety of stimuli, and the activities of several molecules, some developmentally relevant, are directly or indirectly regulated by oxidative stress (active ROS function). Here we review recent data that are suggestive of specific ROS functions during development of animals, particularly mammals.

  11. Reactive oxygen species and antioxidant enzymes activity of Anabaena sp. PCC 7120 (Cyanobacterium) under simulated microgravity.

    PubMed

    Li, Gen-bao; Liu, Yong-ding; Wang, Gao-hong; Song, Li-rong

    2004-12-01

    It was found that reactive oxygen species in Anabaena cells increased under simulated microgravity provided by clinostat. Activities of intracellular antioxidant enzymes, such as superoxide dismutase, catalase were higher than those in the controlled samples during the 7 days' experiment. However, the contents of glutathione [correction of gluathione], an intracellular antioxidant, decreased in comparison with the controlled samples. The results suggested that microgravity provided by clinostat might break the oxidative/antioxidative balance. It indicated a protective mechanism in algal cells, that the total antioxidant system activity increased, which might play an important role for algal cells to adapt the environmental stress of microgravity.

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

    PubMed

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

    2014-08-01

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

  13. Communication: CO oxidation by silver and gold cluster cations: Identification of different active oxygen species

    SciTech Connect

    Popolan, Denisia M.; Bernhardt, Thorsten M.

    2011-03-07

    The oxidation of carbon monoxide with nitrous oxide on mass-selected Au{sub 3}{sup +} and Ag{sub 3}{sup +} clusters has been investigated under multicollision conditions in an octopole ion trap experiment. The comparative study reveals that for both gold and silver cations carbon dioxide is formed on the clusters. However, whereas in the case of Au{sub 3}{sup +} the cluster itself acts as reactive species that facilitates the formation of CO{sub 2} from N{sub 2}O and CO, for silver the oxidized clusters Ag{sub 3}O{sub x}{sup +} (n= 1-3) are identified as active in the CO oxidation reaction. Thus, in the case of the silver cluster cations N{sub 2}O is dissociated and one oxygen atom is suggested to directly react with CO, whereas a second kind of oxygen strongly bound to silver is acting as a substrate for the reaction.

  14. 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.

  15. Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species.

    PubMed

    Chandrasekara, Anoma; Shahidi, Fereidoon

    2011-01-12

    Oxidative stress, caused by reactive oxygen species (ROS), is responsible for modulating several pathological conditions and aging. Soluble and bound phenolic extracts of commonly consumed millets, namely, kodo, finger (Ravi), finger (local), foxtail, proso, little, and pearl, were investigated for their phenolic content and inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS, namely, hydroxyl radical, peroxyl radical, hydrogen peroxide (H(2)O(2)), hypochlorous acid (HOCl), and singlet oxygen ((1)O(2)). Inhibition of DPPH and hydroxyl radicals was detrmined using electron paramagnetic resonance (EPR) spectroscopy. The peroxyl radical inhibitory activity was measured using the oxygen radical absorbance capacity (ORAC) assay. The scavenging of H(2)O(2), HOCl, and (1)O(2) was evaluated using colorimetric methods. The results were expressed as micromoles of ferulic acid equivalents (FAE) per gram of grain on a dry weight basis. In addition, major hydroxycinnamic acids were identified and quantified using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (MS). All millet varieties displayed effective radical and ROS inhibition activities, which generally positively correlated with phenolic contents, except for hydroxyl radical. HPLC analysis revealed the presence of ferulic and p-coumaric acids as major hydroxycinnamic acids in phenolic extract and responsible for the observed effects. Bound extracts of millet contributed 38-99% to ROS scavenging, depending on the variety and the test system employed. Hence, bound phenolics must be included in the evaluation of the antioxidant activity of millets and other cereals.

  16. 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

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

    Weidinger, Adelheid; Kozlov, Andrey V.

    2015-01-01

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

  19. Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells.

    PubMed

    Gremmels, Hendrik; Bevers, Lonneke M; Fledderus, Joost O; Braam, Branko; van Zonneveld, Anton Jan; Verhaar, Marianne C; Joles, Jaap A

    2015-03-15

    Elevated plasma levels of free fatty acids (FFA) are associated with increased cardiovascular risk. This may be related to FFA-induced elevation of oxidative stress in endothelial cells. We hypothesized that, in addition to mitochondrial production of reactive oxygen species, endothelial nitric oxide synthase (eNOS)-mediated reactive oxygen species production contributes to oleic acid (OA)-induced oxidative stress in endothelial cells, due to eNOS uncoupling. We measured reactive oxygen species production and eNOS activity in cultured endothelial cells (bEnd.3) in the presence of OA bound to bovine serum albumin, using the CM-H2DCFDA assay and the L-arginine/citrulline conversion assay, respectively. OA induced a concentration-dependent increase in reactive oxygen species production, which was inhibited by the mitochondrial complex II inhibitor thenoyltrifluoroacetone (TTFA). OA had little effect on eNOS activity when stimulated by a calcium-ionophore, but decreased both basal and insulin-induced eNOS activity, which was restored by TTFA. Pretreatment of bEnd.3 cells with tetrahydrobiopterin (BH4) prevented OA-induced reactive oxygen species production and restored inhibition of eNOS activity by OA. Elevation of OA levels leads to both impairment in receptor-mediated stimulation of eNOS and to production of mitochondrial-derived reactive oxygen species and hence endothelial dysfunction.

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

    PubMed Central

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

    1996-01-01

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

  1. Asbestos-derived reactive oxygen species activate TGF-beta1.

    PubMed

    Pociask, Derek A; Sime, Patricia J; Brody, Arnold R

    2004-08-01

    Transforming growth factor-beta1 (TGF-beta1) is a potent peptide that inhibits epithelial and mesenchymal cell proliferation and stimulates the synthesis of extracellular matrix components. This cytokine is produced in a biologically latent complex bound to a latent-associated peptide (LAP), and it is the disassociation of this complex that regulates TGF-beta activity. A number of mechanisms have been shown to activate TGF-beta1. We show here that reactive oxygen species (ROS), generated by the iron in chrysotile or crocidolite asbestos, mediate the biological activity of TGF-beta1. Recombinant human latent TGF-beta1 was activated in a cell free system in the presence of asbestos and ascorbic acid. Latent TGF-beta1 was overexpressed in both A549 and mink lung epithelial cell lines through an adenovirus vector containing the full-length construct for porcine TGF-beta1. This latent TGF-beta1 was activated in a concentration-dependant fashion by introducing asbestos into the cell cultures. This activation was reduced significantly through the use of superoxide dismutase, catalase or deferoxamine. Amino-acid constituents of the LAP were oxidized as demonstrated by the appearance of carbonyls detected by Western analysis. The oxidized LAP could no longer form a complex with TGF-beta1. Our data support the postulate that ROS derived from asbestos provide a mechanism for activating TGF-beta1 in the alveolar environment by oxidizing amino acids in LAP.

  2. Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function.

    PubMed

    Indo, Hiroko P; Hawkins, Clare L; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Matsui, Hirofumi; Suenaga, Shigeaki; Davies, Michael J; St Clair, Daret K; Ozawa, Toshihiko; Majima, Hideyuki J

    2017-02-08

    Mitochondria are a major source of intracellular energy and reactive oxygen species in cells, but are also increasingly being recognized as a controller of cell death. Here, we review evidence of signal transduction control by mitochondrial superoxide generation via the nuclear factor-κB (NF-κB) and GATA signaling pathways. We have also reviewed the effects of ROS on the activation of MMP and HIF. There is significant evidence to support the hypothesis that mitochondrial superoxide can initiate signaling pathways following transport into the cytosol. In this study, we provide evidence of TATA signal transductions by mitochondrial superoxide. Oxidative phosphorylation via the electron transfer chain, glycolysis, and generation of superoxide from mitochondria could be important factors in regulating signal transduction, cellular homeostasis, and cell death.

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

    PubMed

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

    2013-05-01

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

  4. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling.

    PubMed

    Sena, Laura A; Li, Sha; Jairaman, Amit; Prakriya, Murali; Ezponda, Teresa; Hildeman, David A; Wang, Chyung-Ru; Schumacker, Paul T; Licht, Jonathan D; Perlman, Harris; Bryce, Paul J; Chandel, Navdeep S

    2013-02-21

    It is widely appreciated that T cells increase glycolytic flux during activation, but the role of mitochondrial flux is unclear. Here, we have shown that mitochondrial metabolism in the absence of glucose metabolism is sufficient to support interleukin-2 (IL-2) induction. Furthermore, we used mice with reduced mitochondrial reactive oxygen species (mROS) production in T cells (T-Uqcrfs(-/-) mice) to show that mitochondria are required for T cell activation to produce mROS for activation of nuclear factor of activated T cells (NFAT) and subsequent IL-2 induction. These mice could not induce antigen-specific expansion of T cells in vivo, but Uqcrfs1(-/-) T cells retained the ability to proliferate in vivo under lymphopenic conditions. This suggests that Uqcrfs1(-/-) T cells were not lacking bioenergetically but rather lacked specific ROS-dependent signaling events needed for antigen-specific expansion. Thus, mitochondrial metabolism is a critical component of T cell activation through the production of complex III ROS.

  5. 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

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

    PubMed Central

    2012-01-01

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

  7. 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.

  8. p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation

    PubMed Central

    Jin, Huan; Yin, Shutao; Song, Xinhua; Zhang, Enxiang; Fan, Lihong; Hu, Hongbo

    2016-01-01

    Patulin is a major mycotoxin found in fungal contaminated fruits and their derivative products. Previous studies showed that patulin was able to induce increase of reactive oxygen species (ROS) generation and oxidative stress was suggested to play a pivotal role in patulin-induced multiple toxic signaling. The objective of the present study was to investigate the functional role of p53 in patulin-induced oxidative stress. Our study demonstrated that higher levels of ROS generation and DNA damage were induced in wild-type p53 cell lines than that found in either knockdown or knockout p53 cell lines in response to patulin exposure, suggesting p53 activation contributed to patulin-induced ROS generation. Mechanistically, we revealed that the pro-oxidant role of p53 in response to patulin was attributed to its ability to suppress catalase activity through up-regulation of PIG3. Moreover, these in vitro findings were further validated in the p53 wild-type/knockout mouse model. To the best of our knowledge, this is the first report addressing the functional role of p53 in patulin-induced oxidative stress. The findings of the present study provided novel insights into understanding mechanisms behind oxidative stress in response to patulin exposure. PMID:27071452

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

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy

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

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

    SciTech Connect

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

    2009-04-15

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

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

    SciTech Connect

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

    2014-05-01

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

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

    PubMed

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

    2016-03-01

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

  13. Noninvasive bioluminescence imaging of the dynamics of sanguinarine induced apoptosis via activation of reactive oxygen species

    PubMed Central

    Dai, Yunpeng; Shi, Yaru; Zeng, Qi; Wang, Fu

    2016-01-01

    Most chemotherapeutic drugs exert their anti-tumor effects primarily by triggering a final pathway leading to apoptosis. Noninvasive imaging of apoptotic events in preclinical models would greatly facilitate the development of apoptosis-inducing compounds and evaluation of their therapeutic efficacy. Here we employed a cyclic firefly luciferase (cFluc) reporter to screen potential pro-apoptotic compounds from a number of natural agents. We demonstrated that sanguinarine (SANG) could induce apoptosis in a dose- and time-dependent manner in UM-SCC-22B head and neck cancer cells. Moreover, SANG-induced apoptosis was associated with the generation of reactive oxygen species (ROS) and activation of c-Jun-N-terminal kinase (JNK) and nuclear factor-kappaB (NF-κB) signal pathways. After intravenous administration with SANG in 22B-cFluc xenograft models, a dramatic increase of luminescence signal can be detected as early as 48 h post-treatment, as revealed by longitudinal bioluminescence imaging in vivo. Remarkable apoptotic cells reflected from ex vivo TUNEL staining confirmed the imaging results. Importantly, SANG treatment caused distinct tumor growth retardation in mice compared with the vehicle-treated group. Taken together, our results showed that SANG is a candidate anti-tumor drug and noninvasive imaging of apoptosis using cFluc reporter could provide a valuable tool for drug development and therapeutic efficacy evaluation. PMID:26968950

  14. Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production.

    PubMed

    Yamchuen, Panit; Aimjongjun, Sathid; Limpeanchob, Nanteetip

    2014-12-01

    Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL), but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent patterns and this was accompanied by an increased production of intracellular reactive oxygen species (ROS). Oxidized LDL (10-200 μg/mL) augmented AChE activity after 4 and 24h treatments, respectively while the native LDL was without effect. The increased AChE with oxidized LDLs was accompanied by a proportionate increase in intracellular ROS formation (R=0.904). These findings support the notion that oxidized LDLs are cytotoxic and that their action on AChE may reduce central cholinergic transmission in AD and affirm AChE as a continued rational for anticholinesterase therapy but in conjunction with antioxidant/antihyperlipidemic cotreatments.

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

    SciTech Connect

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

    2011-01-01

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

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

    SciTech Connect

    Wan, Joanne; Winn, Louise M. . E-mail: winnl@queensu.ca

    2007-07-15

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

  17. Using fluorescence-activated flow cytometry to determine reactive oxygen species formation and membrane lipid peroxidation in viable boar spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluorescence-activated flow cytometry analyses were developed for determination of reactive oxygen species (ROS) formation and membrane lipid peroxidation in live spermatozoa loaded with, respectively, hydroethidine (HE) or the lipophilic probe 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-d...

  18. Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis

    PubMed Central

    Liu, Zhe; Lin, Hao; Ye, Sheng; Liu, Qin-ying; Meng, Zhaohui; Zhang, Chuan-mao; Xia, Yongjing; Margoliash, Emanuel; Rao, Zihe; Liu, Xiang-jun

    2006-01-01

    Hydrogen peroxide (H2O2) is the major reactive oxygen species (ROS) produced in sperm. High concentrations of H2O2 in sperm induce nuclear DNA fragmentation and lipid peroxidation and result in cell death. The respiratory chain of the mitochondrion is one of the most productive ROS generating systems in sperm, and thus the destruction of ROS in mitochondria is critical for the cell. It was recently reported that H2O2 generated by the respiratory chain of the mitochondrion can be efficiently destroyed by the cytochrome c-mediated electron-leak pathway where the electron of ferrocytochrome c migrates directly to H2O2 instead of to cytochrome c oxidase. In our studies, we found that mouse testis-specific cytochrome c (T-Cc) can catalyze the reduction of H2O2 three times faster than its counterpart in somatic cells (S-Cc) and that the T-Cc heme has the greater resistance to being degraded by H2O2. Together, these findings strongly imply that T-Cc can protect sperm from the damages caused by H2O2. Moreover, the apoptotic activity of T-Cc is three to five times greater than that of S-Cc in a well established apoptosis measurement system using Xenopus egg extract. The dramatically stronger apoptotic activity of T-Cc might be important for the suicide of male germ cells, considered a physiological mechanism that regulates the number of sperm produced and eliminates those with damaged DNA. Thus, it is very likely that T-Cc has evolved to guarantee the biological integrity of sperm produced in mammalian testis. PMID:16757556

  19. Low energy proton beam induces tumor cell apoptosis through reactive oxygen species and activation of caspases

    PubMed Central

    Lee, Kheun Byeol; Lee, Jong-Soo; Park, Jin-Woo; Huh, Tae-Lin

    2008-01-01

    Proton beam is useful to target tumor tissue sparing normal cells by allowing precise dose only into tumor cells. However, the cellular and molecular mechanisms by which proton beam induces tumor cell death are still undefined. We irradiated three different tumor cells (LLC, HepG2, and Molt-4) with low energy proton beam (35 MeV) with spread out Bragg peak (SOBP) in vitro, and investigated cell death by MTT or CCK-8 assay at 24 h after irradiation. LLC and HepG2 cells were sensitive to proton beam at over 10 Gy to induce apoptosis whereas Molt-4 showed rather low sensitivity. Relative biological effectiveness (RBE) values for the death rate relative to γ-ray were ranged from 1.1 to 2.3 in LLC and HepG2 but from 0.3 to 0.7 in Molt-4 at 11 d after irradiation by colony formation assay. The typical apoptotic nuclear DNA morphological pattern was observed by staining with 4'-6-diamidino-2-phenylindole (DAPI). Tiny fragmented DNA was observed in HepG2 but not in Molt-4 by the treatment of proton in apoptotic DNA fragment assay. By FACS analysis after stained with FITC-Annexin-V, early as well as median apoptotic fractions were clearly increased by proton treatment. Proton beam-irradiated tumor cells induced a cleavage of poly (ADP-ribose) polymerase-1 (PARP-1) and procaspases-3 and -9. Activity of caspases was highly enhanced after proton beam irradiation. Reactive oxygen species (ROS) were significantly increased and N-acetyl cysteine pretreatment restored the apoptotic cell death induced by proton beam. Furthermore, p38 and JNK but not ERK were activated by proton and dominant negative mutants of p38 and JNK revived proton-induced apoptosis, suggesting that p38 and JNK pathway may be activated through ROS to activate apoptosis. In conclusion, our data clearly showed that single treatment of low energy proton beam with SOBP increased ROS and induced cell death of solid tumor cells (LLC and HepG2) in an apoptotic cell death program by the induction of caspases

  20. Effect on active oxygen species of alliin and Allium sativum (garlic) powder.

    PubMed

    Kourounakis, P N; Rekka, E A

    1991-11-01

    Considering that oxygen toxicity and the related free radical attack are involved in many pathophysiological conditions, and that Allium sativum (ASP) has been used therapeutically for many of them since antiquity, we examined the intervention of ASP and alliin in free radical processes. It was found that ASP presented antioxidant activity and alliin was a very good hydroxyl radical scavenger. ASP presented good reducing ability, interacting with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH). These results indicate an involvement of the active Alluim sativum ingredients in free radical processes.

  1. Availability of surface boron species in improved oxygen reduction activity of Pt catalysts: A first-principles study

    NASA Astrophysics Data System (ADS)

    Zhang, Libo; Zhou, Gang

    2016-04-01

    The oxidation process of boron (B) species on the Pt(111) surface and the beneficial effects of boron oxides on the oxygen reduction activity are investigated by first-principles calculations. The single-atom B anchored on the Pt surface has a great attraction for the oxygen species in the immediate environment. With the dissociation of molecular oxygen, a series of boron oxides is formed in succession, both indicating exothermic oxidation reactions. After BO2 is formed, the subsequent O atom immediately participates in the oxygen reduction reaction. The calculated O adsorption energy is appreciably decreased as compared to Pt catalysts, and more approximate to the optimal value of the volcano plot, from which is clear that O hydrogenation kinetics is improved. The modulation mechanism is mainly based on the electron-deficient nature of stable boron oxides, which normally reduces available electronic states of surface Pt atoms that bind the O by facilitating more electron transfer. This modification strategy from the exterior opens the new way, different from the alloying, to efficient electrocatalyst design for PEMFCs.

  2. Protection of mammalian cells by o-phenanthroline from lethal and DNA-damaging effects produced by active oxygen species.

    PubMed

    de Mello Filho, A C; Meneghini, R

    1985-10-30

    Active oxygen species are suspected as being a cause of the cellular damage that occurs at the site of inflammation. Phagocytic cells accumulate at these sites and produce superoxide ion, hydrogen peroxide and hydroxyl radical. The ultimate killing species, the cellular target and the mechanism whereby the lethal injury is produced are unknown. We exposed mouse fibroblasts to xanthine oxidase and acetaldehyde, a system which mimics the membrane of phagocytic cells in terms of production of oxygen species. We observed that the generation of these species produced DNA strand breaks and cellular death. The metal chelator o-phenanthroline completely abolished the former effect, and at the same time it effectively protected the cells from lethal injuries. Because complexing iron o-phenanthroline prevents the formation of hydroxyl radical by the Fendon reaction (Fe(II) + H2O2----Fe(III) + OH- + OH.), it is proposed that most of the cell death and DNA damage are brought about by OH radical, produced from other species by iron-mediated reactions.

  3. Inorganic Polyphosphates Regulate Hexokinase Activity and Reactive Oxygen Species Generation in Mitochondria of Rhipicephalus (Boophilus) microplus Embryo

    PubMed Central

    Fraga, Amanda; Moraes, Jorge; da Silva, José Roberto; Costa, Evenilton P.; Menezes, Jackson; da Silva Vaz Jr, Itabajara; Logullo, Carlos; da Fonseca, Rodrigo Nunes; Campos, Eldo

    2013-01-01

    The physiological roles of polyphosphates (poly P) recently found in arthropod mitochondria remain obscure. Here, the possible involvement of poly P with reactive oxygen species generation in mitochondria of Rhipicephalus microplus embryos was investigated. Mitochondrial hexokinase and scavenger antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione reductase were assayed during embryogenesis of R. microplus. The influence of poly P3 and poly P15 were analyzed during the period of higher enzymatic activity during embryogenesis. Both poly Ps inhibited hexokinase activity by up to 90% and, interestingly, the mitochondrial membrane exopolyphosphatase activity was stimulated by the hexokinase reaction product, glucose-6-phosphate. Poly P increased hydrogen peroxide generation in mitochondria in a situation where mitochondrial hexokinase is also active. The superoxide dismutase, catalase and glutathione reductase activities were higher during embryo cellularization, at the end of embryogenesis and during embryo segmentation, respectively. All of the enzymes were stimulated by poly P3. However, superoxide dismutase was not affected by poly P15, catalase activity was stimulated only at high concentrations and glutathione reductase was the only enzyme that was stimulated in the same way by both poly Ps. Altogether, our results indicate that inorganic polyphosphate and mitochondrial membrane exopolyphosphatase regulation can be correlated with the generation of reactive oxygen species in the mitochondria of R. microplus embryos. PMID:23983617

  4. 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.

  5. 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

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

    SciTech Connect

    Kim, Ki Hyun; Park, Ju Yeol; Jung, Hye Jin; Kwon, Ho Jeong

    2011-01-07

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

  7. The effects of dopamine on antioxidant enzymes activities and reactive oxygen species levels in soybean roots

    PubMed Central

    Gomes, Bruno Ribeiro; Siqueira-Soares, Rita de Cássia; dos Santos, Wanderley Dantas; Marchiosi, Rogério; Soares, Anderson Ricardo; Ferrarese-Filho, Osvaldo

    2014-01-01

    In the current work, we investigated the effects of dopamine, an neurotransmitter found in several plant species on antioxidant enzyme activities and ROS in soybean (Glycine max L. Merrill) roots. The effects of dopamine on SOD, CAT and POD activities, as well as H2O2, O2•−, melanin contents and lipid peroxidation were evaluated. Three-day-old seedlings were cultivated in half-strength Hoagland nutrient solution (pH 6.0), without or with 0.1 to 1.0 mM dopamine, in a growth chamber (25°C, 12 h photoperiod, irradiance of 280 μmol m−2 s−1) for 24 h. Significant increases in melanin content were observed. The levels of ROS and lipid peroxidation decreased at all concentrations of dopamine tested. The SOD activity increased significantly under the action of dopamine, while CT activity was inhibited and POD activity was unaffected. The results suggest a close relationship between a possible antioxidant activity of dopamine and melanin and activation of SOD, reducing the levels of ROS and damage on membranes of soybean roots. PMID:25482756

  8. Identification of carbon-encapsulated iron nanoparticles as active species in non-precious metal oxygen reduction catalysts

    PubMed Central

    Varnell, Jason A.; Tse, Edmund C. M.; Schulz, Charles E.; Fister, Tim T.; Haasch, Richard T.; Timoshenko, Janis; Frenkel, Anatoly I.; Gewirth, Andrew A.

    2016-01-01

    The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts. Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments. In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using Mössbauer and X-ray absorption spectroscopy. Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst. These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites. PMID:27538720

  9. Identification of carbon-encapsulated iron nanoparticles as active species in non-precious metal oxygen reduction catalysts.

    PubMed

    Varnell, Jason A; Tse, Edmund C M; Schulz, Charles E; Fister, Tim T; Haasch, Richard T; Timoshenko, Janis; Frenkel, Anatoly I; Gewirth, Andrew A

    2016-08-19

    The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts. Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments. In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using Mössbauer and X-ray absorption spectroscopy. Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst. These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites.

  10. Identification of carbon-encapsulated iron nanoparticles as active species in non-precious metal oxygen reduction catalysts

    NASA Astrophysics Data System (ADS)

    Varnell, Jason A.; Tse, Edmund C. M.; Schulz, Charles E.; Fister, Tim T.; Haasch, Richard T.; Timoshenko, Janis; Frenkel, Anatoly I.; Gewirth, Andrew A.

    2016-08-01

    The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active species in non-precious metal catalysts remains elusive, impeding the development of new catalysts. Here we demonstrate the reversible deactivation and reactivation of an iron-based non-precious metal oxygen reduction catalyst achieved using high-temperature gas-phase chlorine and hydrogen treatments. In addition, we observe a decrease in catalyst heterogeneity following treatment with chlorine and hydrogen, using Mössbauer and X-ray absorption spectroscopy. Our study reveals that protected sites adjacent to iron nanoparticles are responsible for the observed activity and stability of the catalyst. These findings may allow for the design and synthesis of enhanced non-precious metal oxygen reduction catalysts with a higher density of active sites.

  11. Aging Enhances the Production of Reactive Oxygen Species and Bactericidal Activity in Peritoneal Macrophages by Upregulating Classical Activation Pathways

    SciTech Connect

    Smallwood, Heather S.; López-Ferrer, Daniel; Squier, Thomas C.

    2011-10-07

    . Collectively, these results indicate that macrophages isolated from old mice are in a preactivated state that enhances their sensitivities to LPS exposure. The hyper-responsive activation of macrophages in aged animals may act to minimize infection by general bacterial threats that arise due to age-dependent declines in adaptive immunity. Finally, however, this hypersensitivity and the associated increase in the level of formation of reactive oxygen species are likely to contribute to observed age-dependent increases in the level of oxidative damage that underlie many diseases of the elderly.

  12. Aging enhances the production of reactive oxygen species and bactericidal activity in peritoneal macrophages by upregulating classical activation pathways.

    PubMed

    Smallwood, Heather S; López-Ferrer, Daniel; Squier, Thomas C

    2011-11-15

    . Collectively, these results indicate that macrophages isolated from old mice are in a preactivated state that enhances their sensitivities to LPS exposure. The hyper-responsive activation of macrophages in aged animals may act to minimize infection by general bacterial threats that arise due to age-dependent declines in adaptive immunity. However, this hypersensitivity and the associated increase in the level of formation of reactive oxygen species are likely to contribute to observed age-dependent increases in the level of oxidative damage that underlie many diseases of the elderly.

  13. 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

  14. 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.

  15. Hyperosmotic stress-dependent NFkappaB activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes.

    PubMed

    Eisner, Verónica; Criollo, Alfredo; Quiroga, Clara; Olea-Azar, Claudio; Santibañez, Juan Francisco; Troncoso, Rodrigo; Chiong, Mario; Díaz-Araya, Guillermo; Foncea, Rocío; Lavandero, Sergio

    2006-08-07

    We have recently shown that hyperosmotic stress activates p65/RelB NFkappaB in cultured cardiomyocytes with dichotomic actions on caspase activation and cell death. It remains unexplored how NFkappaB is regulated in cultured rat cardiomyocytes exposed to hyperosmotic stress. We study here: (a) if hyperosmotic stress triggers reactive oxygen species (ROS) generation and in turn whether they regulate NFkappaB and (b) if insulin-like growth factor-1 (IGF-1) modulates ROS production and NFkappaB activation in hyperosmotically-stressed cardiomyocytes. The results showed that hyperosmotic stress generated ROS in cultured cardiac myocytes, in particular the hydroxyl and superoxide species, which were inhibited by N-acetylcysteine (NAC). Hyperosmotic stress-induced NFkappaB activation as determined by IkappaBalpha degradation and NFkappaB DNA binding. NFkappaB activation and procaspase-3 and -9 fragmentation were prevented by NAC and IGF-1. However, this growth factor did not decrease ROS generation induced by hyperosmotic stress, suggesting that its actions over NFkappaB and caspase activation may be due to modulation of events downstream of ROS generation. We conclude that hyperosmotic stress induces ROS, which in turn activates NFkappaB and caspases. IGF-1 prevents NFkappaB activation by a ROS-independent mechanism.

  16. Pentosidine in advanced glycation end-products (AGEs) during UVA irradiation generates active oxygen species and impairs human dermal fibroblasts.

    PubMed

    Okano, Y; Masaki, H; Sakurai, H

    2001-08-01

    Our previous study reported that advanced glycation end-products (AGE)-modified BSA produced active oxygen species, *O2-, H2O2, and *OH under UVA irradiation and enhanced the cytotoxicity of UVA light. We examined whether pentosidine in AGE-modified BSA was involved in one of the mechanisms generating the active oxygen species. In biological investigations, fibroblasts exposed to UVA (20 J/cm2) in the presence of pentosidine-rich compounds (PRCs), which were prepared with L-arginine, L-lysine and glucose, showed a time-dependent leakage of the cytosolic enzyme LDH. In addition, release of LDH was suppressed by addition of DMSO and deferoxamine under UVA irradiation. From these results, it was determined that PRCs exposed to UVA damaged the plasma membrane of human dermal fibroblasts due to the conversion of *OH from H2O2 via a Fenton-like reaction. These features of PRCs exposed to UVA were consistent with those of AGE-modified BSA. In an ESR study, PRCs under UVA irradiation yielded DMPO-OH (DMPO-OH adduct) using DMPO as a spin-trapping reagent. *O2- generation from UVA-irradiated PRCs was also indicated by the combination of NBT reduction and SOD. When PRCs were exposed to UVA light controlled with a long-pass filter, WG-360, it was found that their production of *O2- was prohibited less than 50% in the NBT reduction assay. The *O2- production profile of PRCs depending on the wavelength of UVA light was similar to that of AGE-modified BSA. Furthermore, it was found that the H2O2 level was increased by PRCs exposed to UVA. These results indicated that pentosidine is an important factor of AGE-modified BSA in active oxygen generation under UVA irradiation.

  17. XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species.

    PubMed

    Rezvani, Hamid Reza; Rossignol, Rodrigue; Ali, Nsrein; Benard, Giovanni; Tang, Xiuwei; Yang, Hee Seung; Jouary, Thomas; de Verneuil, Hubert; Taïeb, Alain; Kim, Arianna L; Mazurier, Frédéric

    2011-06-01

    Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the inter-relationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPC(KD)) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers.

  18. XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species

    PubMed Central

    Rezvani, Hamid Reza; Rossignol, Rodrigue; Ali, Nsrein; Benard, Giovanni; Tang, Xiuwei; Yang, Hee Seung; Jouary, Thomas; de Verneuil, Hubert; Taïeb, Alain; Kim, Arianna L.; Mazurier, Frédéric

    2011-01-01

    Summary Cancer cells utilize complex mechanisms to remodel their bioenergetic properties. We exploited the intrinsic genomic stability of xeroderma pigmentosum C (XPC) to understand the interrelationships between genomic instability, reactive oxygen species (ROS) generation, and metabolic alterations during neoplastic transformation. We showed that knockdown of XPC (XPCKD) in normal human keratinocytes results in metabolism remodeling through NADPH oxidase-1 (NOX-1) activation, which in turn leads to increased ROS levels. While enforcing antioxidant defenses by overexpressing catalase, CuZnSOD, or MnSOD could not block the metabolism remodeling, impaired NOX-1 activation abrogates both alteration in ROS levels and modifications of energy metabolism. As NOX-1 activation is observed in human squamous cell carcinomas (SCCs), the blockade of NOX-1 could be a target for the prevention and the treatment of skin cancers. PMID:21167810

  19. Calpain and Reactive Oxygen Species Targets Bax for Mitochondrial Permeabilisation and Caspase Activation in Zerumbone Induced Apoptosis

    PubMed Central

    Sobhan, Praveen K.; Seervi, Mahendra; Deb, Lokesh; Varghese, Saneesh; Soman, Anjana; Joseph, Jeena; Mathew, Krupa Ann; Raghu, Godi; Thomas, George; E, Sreekumar; S, Manjula; R, Santosh Kumar T.

    2013-01-01

    Fluorescent protein based signaling probes are emerging as valuable tools to study cell signaling because of their ability to provide spatio- temporal information in non invasive live cell mode. Previously, multiple fluorescent protein probes were employed to characterize key events of apoptosis in diverse experimental systems. We have employed a live cell image based approach to visualize the key events of apoptosis signaling induced by zerumbone, the active principle from ginger Zingiber zerumbet, in cancer cells that enabled us to analyze prominent apoptotic changes in a hierarchical manner with temporal resolution. Our studies substantiate that mitochondrial permeabilisation and cytochrome c dependent caspase activation dominate in zerumbone induced cell death. Bax activation, the essential and early event of cell death, is independently activated by reactive oxygen species as well as calpains. Zerumbone failed to induce apoptosis or mitochondrial permeabilisation in Bax knockout cells and over-expression of Bax enhanced cell death induced by zerumbone confirming the essential role of Bax for mitochondrial permeabilsation. Simultaneous inhibition of reactive oxygen species and calpain is required for preventing Bax activation and cell death. However, apoptosis induced by zerumbone was prevented in Bcl 2 and Bcl-XL over-expressing cells, whereas more protection was afforded by Bcl 2 specifically targeted to endoplasmic reticulum. Even though zerumbone treatment down-regulated survival proteins such as XIAP, Survivin and Akt, it failed to affect the pro-apoptotic proteins such as PUMA and BIM. Multiple normal diploid cell lines were employed to address cytotoxic activity of zerumbone and, in general, mammary epithelial cells, endothelial progenitor cells and smooth muscle cells were relatively resistant to zerumbone induced cell death with lesser ROS accumulation than cancer cells. PMID:23593137

  20. Fullerene (C60) nanoparticles exert photocytotoxicity through modulation of reactive oxygen species and p38 mitogen-activated protein kinase activation in the MCF-7 cancer cell line

    NASA Astrophysics Data System (ADS)

    Li, Zhi; Zhang, Fei-long; Wang, Zhiyuan; Pan, Li-li; Shen, Ying-ying; Zhang, Zhen-zhong

    2013-12-01

    The photocytotoxicity of water-dispersed 100-300 nm fullerene amino acid derivatives nanoparticles was studied. The nanoparticle solution of fullerene derivatives, l-phenylalanine (C60-phe) and glycine (C60-gly), suppressed the in vitro growth of MCF-7 cells lines, induced cancer cells apoptosis, and caused a perturbation of the cell cycle. These nanoparticle solutions increased intracellular reactive oxygen species after irradiation. C60-phe or C60-gly upregulated the expression of phosphorylated (p)p38 mitogen-activated protein kinase (MAPK). N-Acetyl- l-cysteine significantly depressed the composite-induced activation of p38MAPK, and the kinase inhibitor SB203580 significantly prevented C60 derivative-induced cell apoptosis. This study revealed that p38MAPK is activated by C60 nanoparticles through triggering reactive oxygen species generation, leading to cancer cell injuries.

  1. Synthesis of SiC/Ag/Cellulose Nanocomposite and Its Antibacterial Activity by Reactive Oxygen Species Generation

    PubMed Central

    Borkowski, Andrzej; Cłapa, Tomasz; Szala, Mateusz; Gąsiński, Arkadiusz; Selwet, Marek

    2016-01-01

    We describe the synthesis of nanocomposites, based on nanofibers of silicon carbide, silver nanoparticles, and cellulose. Silver nanoparticle synthesis was achieved with chemical reduction using hydrazine by adding two different surfactants to obtain a nanocomposite with silver nanoparticles of different diameters. Determination of antibacterial activity was based on respiration tests. Enzymatic analysis indicates oxidative stress, and viability testing was conducted using an epifluorescence microscope. Strong bactericidal activity of nanocomposites was found against bacteria Escherichia coli and Bacillus cereus, which were used in the study as typical Gram-negative and Gram-positive bacteria, respectively. It is assumed that reactive oxygen species generation was responsible for the observed antibacterial effect of the investigated materials. Due to the properties of silicon carbide nanofiber, the obtained nanocomposite may have potential use in technology related to water and air purification. Cellulose addition prevented silver nanoparticle release and probably enhanced bacterial adsorption onto aggregates of the nanocomposite material. PMID:28335299

  2. 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

  3. Contribution of transition metals in the reactive oxygen species activity of PM emissions from retrofitted heavy-duty vehicles

    NASA Astrophysics Data System (ADS)

    Verma, Vishal; Shafer, Martin M.; Schauer, James J.; Sioutas, Constantinos

    2010-12-01

    We assessed the contribution of water-soluble transition metals to the reactive oxygen species (ROS) activity of diesel exhaust particles (DEPs) from four heavy-duty vehicles in five retrofitted configurations (V-SCRT, Z-SCRT, DPX, hybrid, and school bus). A heavy-duty truck without any control device served as the baseline vehicle. Particles were collected from all vehicle-configurations on a chassis dynamometer under three driving conditions: cruise (80 km h -1), transient UDDS, and idle. A sensitive macrophage-based in vitro assay was used to determine the ROS activity of collected particles. The contribution of water-soluble transition metals in the measured activity was quantified by their removal using a Chelex ® complexation method. The study demonstrates that despite an increase in the intrinsic ROS activity (per mass basis) of exhaust PM with use of most control technologies, the overall ROS activity (expressed per km or per h) was substantially reduced for retrofitted configurations compared to the baseline vehicle. Chelex treatment of DEPs water extracts removed a substantial (≥70%) and fairly consistent fraction of the ROS activity, which ascertains the dominant role of water-soluble metals in PM-induced cellular oxidative stress. However, relatively lower removal of the activity in few vehicle-configurations (V-SCRT, DPX and school bus idle), despite a large aggregate metals removal, indicated that not all species were associated with the measured activity. A univariate regression analysis identified several transition metals (Fe, Cr, Co and Mn) as significantly correlated ( R > 0.60; p < 0.05) with the ROS activity. Multivariate linear regression model incorporating Fe, Cr and Co explained 90% of variability in ROS levels, with Fe accounting for the highest (84%) fraction of the variance.

  4. In Situ Observation of Active Oxygen Species in Fe-Containing Ni-Based Oxygen Evolution Catalysts: The Effect of pH on Electrochemical Activity.

    PubMed

    Trześniewski, Bartek J; Diaz-Morales, Oscar; Vermaas, David A; Longo, Alessandro; Bras, Wim; Koper, Marc T M; Smith, Wilson A

    2015-12-09

    Ni-based oxygen evolution catalysts (OECs) are cost-effective and very active materials that can be potentially used for efficient solar-to-fuel conversion process toward sustainable energy generation. We present a systematic spectroelectrochemical characterization of two Fe-containing Ni-based OECs, namely nickel borate (Ni(Fe)-B(i)) and nickel oxyhydroxide (Ni(Fe)OOH). Our Raman and X-ray absorption spectroscopy results show that both OECs are chemically similar, and that the borate anions do not play an apparent role in the catalytic process at pH 13. Furthermore, we show spectroscopic evidence for the generation of negatively charged sites in both OECs (NiOO(-)), which can be described as adsorbed "active oxygen". Our data conclusively links the OER activity of the Ni-based OECs with the generation of those sites on the surface of the OECs. The OER activity of both OECs is strongly pH dependent, which can be attributed to a deprotonation process of the Ni-based OECs, leading to the formation of the negatively charged surface sites that act as OER precursors. This work emphasizes the relevance of the electrolyte effect to obtain catalytically active phases in Ni-based OECs, in addition to the key role of the Fe impurities. This effect should be carefully considered in the development of Ni-based compounds meant to catalyze the OER at moderate pHs. Complementarily, UV-vis spectroscopy measurements show strong darkening of those catalysts in the catalytically active state. This coloration effect is directly related to the oxidation of nickel and can be an important factor limiting the efficiency of solar-driven devices utilizing Ni-based OECs.

  5. Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production

    SciTech Connect

    Chung, Jin Sil; Lee, Sora; Yoo, Young Do

    2014-08-08

    Highlights: • Romo1 expression is required for constitutive nuclear DNA-binding activity of NF-κB. • Romo1 depletion suppresses tumor growth in vivo. • Romo1 presents a potential therapeutic target for diseases. - Abstract: Deregulation of nuclear factor-κB (NF-κB) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-κB activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclear DNA-binding activity of NF-κB and transcriptional activity through constitutive IκBα phosphorylation. Overexpression of Romo1 promoted p65 nuclear translocation and DNA-binding activity. We also show that Romo1 depletion suppressed anchorage-independent colony formation by HCC cells and suppressed tumor growth in vivo. Based on these findings, Romo1 may be a principal regulatory factor in the maintenance of constitutive NF-κB activation in tumor cells. In the interest of anti-proliferative treatments for cancer, Romo1 may also present a productive target for drug development.

  6. ARSENIC SPECIES THAT CAUSE RELEASE OF IRON FROM FERRITIN AND GENERATION OF ACTIVATED OXYGEN

    EPA Science Inventory


    ABSTRACT

    The in vitro effects of four different species of arsenic { arsenate, arsenite, monomethylarsonic acid and dimethylarsinic acid) in mobilizing iron from horse spleen ferritin under aerobic and anaerobic conditions were investigated. Dimethylarsinicacid {DMA(V...

  7. Wood dusts induce the production of reactive oxygen species and caspase-3 activity in human bronchial epithelial cells.

    PubMed

    Pylkkänen, Lea; Stockmann-Juvala, Helene; Alenius, Harri; Husgafvel-Pursiainen, Kirsti; Savolainen, Kai

    2009-08-21

    Wood dusts are associated with several respiratory symptoms, e.g. impaired lung function and asthma, in exposed workers. However, despite the evidence from epidemiological studies, the underlying mechanisms are not well understood. In the present study, we investigated different wood dusts for their capacity to induce cytotoxicity and production of radical oxygen species (ROS) as well as activation of the apoptotic caspase-3 enzyme in human bronchial epithelial cells (BEAS-2B). Dusts from three different tree species widely used in wood industry were studied; birch and oak represented hardwood species, and pine a common softwood species. All the experiments were carried out in three different concentrations (10, 50, and 500 microg/ml) and the analysis was performed after 0.5, 2, 6, and 24h exposure. All wood dusts studied were cytotoxic to human bronchial epithelial cells in a dose-dependent manner after 2 and 6h treatment. Exposure to pine, birch, or oak dust had a significant stimulating effect on the production of ROS. Also an induction in caspase-3 protease activity, one of the central components of the apoptotic cascade, was seen in BEAS-2B cells after 2 and 6h exposure to each of the wood dusts studied. In summary, we demonstrate that dusts from pine, birch and oak are cytotoxic, able to increase the production of ROS and the apoptotic response in human broncho-epithelial cells in vitro. Thus, our current data suggest oxidative stress by ROS as an important mechanism likely to function in wood dust related pulmonary toxicity although details of the cellular targets and cell-particle interactions remain to be solved. It is though tempting to speculate that redox-regulated transcription factors such as NFkappaB or AP-1 may play a role in this wood dust-evoked process leading to apparently induced apoptosis of target cells.

  8. 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.

  9. Influence of Reactive Oxygen Species on the Enzyme Stability and Activity in the Presence of Ionic Liquids

    PubMed Central

    Attri, Pankaj; Choi, Eun Ha

    2013-01-01

    In this paper, we have examined the effect of ammonium and imidazolium based ionic liquids (ILs) on the stability and activity of proteolytic enzyme α-chymotrypsin (CT) in the presence of cold atmospheric pressure plasma jet (APPJ). The present work aims to illustrate the state of art implementing the combined action of ILs and APPJ on the enzyme stability and activity. Our circular dichroism (CD), fluorescence and enzyme activity results of CT have revealed that buffer and all studied ILs {triethylammonium hydrogen sulphate (TEAS) from ammonium family and 1-butyl-3-methyl imidazolium chloride ([Bmim][Cl]), 1-methylimidazolium chloride ([Mim][Cl]) from imidazolium family} are notable to act as protective agents against the deleterious action of the APPJ, except triethylammonium dihydrogen phosphate (TEAP) ammonium IL. However, TEAP attenuates strongly the deleterious action of reactive oxygen species (ROS) created by APPJ on native structure of CT. Further, TEAP is able to retain the enzymatic activity after APPJ exposure which is absent in all the other systems.This study provides the first combined effect of APPJ and ILs on biomolecules that may generate many theoretical and experimental opportunities. Through this methodology, we can utilise both enzyme and plasma simultaneously without affecting the enzyme structure and activity on the material surface; which can prove to be applicable in various fields. PMID:24066167

  10. Zinc wave during the treatment of hypoxia is required for initial reactive oxygen species activation in mitochondria

    PubMed Central

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

    2016-01-01

    Mitochondrial reactive oxygen species (ROS) are known to accumulate during chemical hypoxia, causing adverse effects on cell function and survival. Recent studies show important role zinc accumulation plays in dysfunction associated with hypoxia. It is well known that ROS accumulation also plays a major role in cellular damage by hypoxia. In this study, fluorescent imaging and pharmacological methods were used in live HeLa cells to determine role of zinc in initial ROS accumulation in mitochondria during chemical hypoxia (oxygen glucose depravation with 4 mM sodium dithionite). Accumulation of both was observed as a very rapid phenomenon with initial rapid zinc increase (zinc wave) within 60 seconds of hypoxia onset and ROS increase within 4.5 minutes. Zinc chelation with TPEN removed the initial zinc wave which in turn abolished ROS accumulation. Influx of exogenous zinc induced rapid ROS accumulation. Inhibition of NADPH oxidase with apocynin, a NADPH oxidase inhibitor, showed significant and prolonged reduction in zinc induced ROS accumulation. We proposed a novel mechanism of intracellular zinc increase that activates NADPH oxidase which in turn triggers mitochondrial ROS production. PMID:27186322

  11. Promoting Active Species Generation by Electrochemical Activation in Alkaline Media for Efficient Electrocatalytic Oxygen Evolution in Neutral Media.

    PubMed

    Xu, Kun; Cheng, Han; Liu, Linqi; Lv, Haifeng; Wu, Xiaojun; Wu, Changzheng; Xie, Yi

    2017-01-11

    In this study, by using dicobalt phosphide nanoparticles as precatalysts, we demonstrated that electrochemical activation of metallic precatalysts in alkaline media (comparing with directly electrochemical activation in neutral media) could significantly promote the OER catalysis in neutral media, specifically realizing a 2-fold enhanced activity and meanwhile showing a greatly decreased overpotential of about 100 mV at 10 mA cm(-2). Compared directly with electrochemical activation in neutral media, the electrochemical activation in harsh alkaline media could easily break the strong Co-Co bond and promote active species generation on the surface of metallic Co2P, thus accounting for the enhancement of neutral OER activity, which is also evidenced by HRTEM and the electrochemical double-layer capacitance measurement. The activation of electrochemical oxidation of metallic precatalysts in alkaline media enhanced neutral OER catalysis could also be observed on CoP nanoparticles and Ni2P nanoparticles, suggesting this is a generic strategy. Our work highlights that the activation of electrochemical oxidation of metallic precatalysts in alkaline media would pave new avenues for the design of advanced neutral OER electrocatalysts.

  12. Xanthohumol induces apoptosis in human malignant glioblastoma cells by increasing reactive oxygen species and activating MAPK pathways.

    PubMed

    Festa, Michela; Capasso, Anna; D'Acunto, Cosimo W; Masullo, Milena; Rossi, Adriano G; Pizza, Cosimo; Piacente, Sonia

    2011-12-27

    The effect of the biologically active prenylated chalcone and potential anticancer agent xanthohumol (1) has been investigated on apoptosis of the T98G human malignant glioblastoma cell line. Compound 1 decreased the viability of T98G cells by induction of apoptosis in a time- and concentration-dependent manner. Apoptosis induced by 1 was associated with activation of caspase-3, caspase-9, and PARP cleavage and was mediated by the mitochondrial pathway, as exemplified by mitochondrial depolarization, cytochrome c release, and downregulation of the antiapoptotic Bcl-2 protein. Xanthohumol induced intracellular reactive oxygen species (ROS), an effect that was reduced by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). Intracellular ROS production appeared essential for the activation of the mitochondrial pathway and induction of apoptosis after exposure to 1. Oxidative stress due to treatment with 1 was associated with MAPK activation, as determined by ERK1/2 and p38 phosphorylation. Phosphorylation of ERK1/2 and p38 was attenuated using NAC to inhibit ROS production. After treatment with 1, ROS provided a specific environment that resulted in MAPK-induced cell death, with this effect reduced by the ERK1/2 specific inhibitor PD98059 and partially inhibited by the p38 inhibitor SB203580. These findings suggest that xanthohumol (1) is a potential chemotherapeutic agent for the treatment of glioblastoma multiforme.

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

    PubMed

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

    2016-05-23

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

  14. Low level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts

    NASA Astrophysics Data System (ADS)

    Chen, Aaron Chih-Hao; Arany, Praveen R.; Huang, Ying-Ying; Tomkinson, Elizabeth M.; Saleem, Taimur; Yull, Fiona E.; Blackwell, Timothy S.; Hamblin, Michael R.

    2009-02-01

    Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation remain unclear. In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810-nm laser radiation. Significant activation of NFkB was observed for fluences higher than 0.003 J/cm2. NF-kB activation by laser was detectable at 1-hour time point. Moreover, we demonstrated that laser phosphorylated both IKK α/β and NF-kB 15 minutes after irradiation, which implied that laser activates NF-kB via phosphorylation of IKK α/β. Suspecting mitochondria as the source of NF-kB activation signaling pathway, we demonstrated that laser increased both intracellular reactive oxygen species (ROS) by fluorescence microscopy with dichlorodihydrofluorescein and ATP synthesis by luciferase assay. Mitochondrial inhibitors, such as antimycin A, rotenone and paraquat increased ROS and NF-kB activation but had no effect on ATP. The ROS quenchers N-acetyl-L-cysteine and ascorbic acid abrogated laser-induced NF-kB and ROS but not ATP. These results suggested that ROS might play an important role in the signaling pathway of laser induced NF-kB activation. However, the western blot showed that antimycin A, a mitochondrial inhibitor, did not activate NF-kB via serine phosphorylation of IKK α/β as the laser did. On the other hand, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that light also upregulates mitochondrial respiration. ATP upregulation reached a maximum at 0.3 J/cm2 or higher. We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive transcription factor NF-kB by generating ROS as signaling molecules.

  15. Reactive oxygen species are involved in arsenic trioxide inhibition of pyruvate dehydrogenase activity.

    PubMed

    Samikkannu, Thangavel; Chen, Chien-Hung; Yih, Ling-Huei; Wang, Alexander S S; Lin, Shu-Yu; Chen, Tsen-Chien; Jan, Kun-Yan

    2003-03-01

    Arsenite was shown to inhibit pyruvate dehydrogenase (PDH) activity through binding to vicinal dithiols in pure enzyme and tissue extract. However, no data are available on how arsenite inhibits PDH activity in human cells. The IC(50) values for arsenic trioxide (As(2)O(3)) to inhibit the PDH activity in porcine heart pure enzyme preparation and in human leukemia cell line HL60 cells were estimated to be 182 and 2 microM, respectively. Thus, As(2)O(3) inactivation of PDH activity was about 90 times more potent in HL60 cells than in purified enzyme preparation. The IC(50) values for As(2)O(3) and phenylarsine oxide to reduce the vicinal thiol content in HL60 cells were estimated to be 81.7 and 1.9 microM, respectively. Thus, As(2)O(3) is a potent PDH inhibitor but a weak vicinal thiol reacting agent in HL60 cells. Antioxidants but not dithiol compounds suppressed As(2)O(3) inhibition of PDH activity in HL60 cells. Conversely, dithiol compounds but not antioxidants suppressed the inhibition of PDH activity by phenylarsine oxide. As(2)O(3) increased H(2)O(2) level in HL60 cells, but this was not observed for phenylarsine oxide. Mitochondrial respiration inhibitors suppressed the As(2)O(3)-induced H(2)O(2) production and As(2)O(3) inhibition of PDH activity. Moreover, metal chelators ameliorated whereas Fenton metals aggravated As(2)O(3) inhibition of PDH activity. Treatment with H(2)O(2) plus Fenton metals also decreased the PDH activity in HL60 cells. Therefore, it seems that As(2)O(3) elevates H(2)O(2) production in mitochondria and this may produce hydroxyl through the Fenton reaction and result in oxidative damage to the protein of PDH. The present results suggest that arsenite may cause protein oxidation to inactivate an enzyme and this can occur at a much lower concentration than arsenite binding directly to the critical thiols.

  16. Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner

    PubMed Central

    Daijo, Hiroki; Hoshino, Yuma; Kai, Shinichi; Suzuki, Kengo; Nishi, Kenichiro; Matsuo, Yoshiyuki; Harada, Hiroshi; Hirota, Kiichi

    2016-01-01

    Cigarette smoke (CS) is a major contributor to the development of a large number of fatal and debilitating disorders. However, the precise molecular mechanisms underlying the effects of CS in lung disease are largely unknown. To elucidate these pathophysiological processes, we examined the in vitro and in vivo effects of CS extract (CSE) and CS on the transcription factor, hypoxia-inducible factor 1 (HIF-1). CSE induced concentration- and time-dependent accumulation of HIF-1α protein in human lung epithelial-like cells under non-hypoxic conditions. Genes upregulated by HIF-1, including vascular endothelial growth factor and regulated in development and DNA damage response 1, both of which are involved in smoking-induced emphysematous changes, were increased by CSE treatment under non-hypoxic conditions in vitro and in vivo. Further investigation revealed that reactive oxygen species were generated in cells exposed to CSE and were required for CSE-mediated induction of HIF-1α protein, as was activation of phosphoinositide 3-kinase and mitogen-activated protein kinase pathways. In conclusion, we demonstrated that CSE and CS induced HIF-1 activation in vitro and in vivo, respectively. The evidence warrants further investigation to indicate that HIF-1 plays an important role in CS-induced gene expression, which is deeply involved in pulmonary cellular stress and small airway remodelling. PMID:27680676

  17. Glibenclamide decreases ATP-induced intracellular calcium transient elevation via inhibiting reactive oxygen species and mitochondrial activity in macrophages.

    PubMed

    Li, Duo-ling; Ma, Zhi-yong; Fu, Zhi-jie; Ling, Ming-ying; Yan, Chuan-zhu; Zhang, Yun

    2014-01-01

    Increasing evidence has revealed that glibenclamide has a wide range of anti-inflammatory effects. However, it is unclear whether glibenclamide can affect the resting and adenosine triphosphate (ATP)-induced intracellular calcium ([Ca(2+)]i) handling in Raw 264.7 macrophages. In the present study, [Ca(2+)]i transient, reactive oxygen species (ROS) and mitochondrial activity were measured by the high-speed TILLvisION digital imaging system using the indicators of Fura 2-am, DCFDA and rhodamine-123, respectively. We found that glibenclamide, pinacidil and other unselective K(+) channel blockers had no effect on the resting [Ca(2+)]i of Raw 264.7 cells. Extracellular ATP (100 µM) induced [Ca(2+)]i transient elevation independent of extracellular Ca(2+). The transient elevation was inhibited by an ROS scavenger (tiron) and mitochondria inhibitor (rotenone). Glibenclamide and 5-hydroxydecanoate (5-HD) also decreased ATP-induced [Ca(2+)]i transient elevation, but pinacidil and other unselective K(+) channel blockers had no effect. Glibenclamide also decreased the peak of [Ca(2+)]i transient induced by extracellular thapsigargin (Tg, 1 µM). Furthermore, glibenclamide decreased intracellular ROS and mitochondrial activity. When pretreated with tiron and rotenone, glibenclamide could not decrease ATP, and Tg induced maximal [Ca(2+)]i transient further. We conclude that glibenclamide may inhibit ATP-induced [Ca(2+)]i transient elevation by blocking mitochondria KATP channels, resulting in decreased ROS generation and mitochondrial activity in Raw 264.7 macrophages.

  18. Reactive Oxygen Species and Nuclear Factor Erythroid 2-Related Factor 2 Activation in Diabetic Nephropathy: A Hidden Target

    PubMed Central

    Abdo, Shaaban; Zhang, Shao-Ling; Chan, John S.D.

    2015-01-01

    Hyperglycemia, oxidative stress and renin-angiotensin system (RAS) dysfunction have been implicated in diabetic nephropathy (DN) progression, but the underlying molecular mechanisms are far from being fully understood. In addition to the systemic RAS, the existence of a local intrarenal RAS in renal proximal tubular cells has been recognized. Angiotensinogen is the sole precursor of all angiotensins (Ang). Intrarenal reactive oxygen species (ROS) generation, Ang II level and RAS gene expression are up-regulated in diabetes, indicating that intrarenal ROS and RAS activation play an important role in DN. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is one of the major protective processes that occurs in response to intracellular oxidative stress. Nrf2 stimulates an array of antioxidant enzymes that convert excessive ROS to less reactive or less damaging forms. Recent studies have, however, revealed that Nrf2 activation might have other undesirable effects in diabetic animals and in diabetic patients with chronic kidney disease. This mini-review summarizes current knowledge of the relationship between ROS, Nrf2 and intra renal RAS activation in DN progression as well as possible novel target(s) for DN treatment. PMID:26213634

  19. Lysophosphatidic acid induces reactive oxygen species generation by activating protein kinase C in PC-3 human prostate cancer cells

    SciTech Connect

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien; Ju, Tsai-Kai; Huang, Yuan-Li; Lee, Ming-Shyue; Chen, Jiun-Hong; Lee, Hsinyu

    2013-11-01

    Highlights: •LPA induces ROS generation through LPA{sub 1} and LPA{sub 3}. •LPA induces ROS generation by activating PLC. •PKCζ mediates LPA-induced ROS generation. -- Abstract: Prostate cancer is one of the most frequently diagnosed cancers in males, and PC-3 is a cell model popularly used for investigating the behavior of late stage prostate cancer. Lysophosphatidic acid (LPA) is a lysophospholipid that mediates multiple behaviors in cancer cells, such as proliferation, migration and adhesion. We have previously demonstrated that LPA enhances vascular endothelial growth factor (VEGF)-C expression in PC-3 cells by activating the generation of reactive oxygen species (ROS), which is known to be an important mediator in cancer progression. Using flow cytometry, we showed that LPA triggers ROS generation within 10 min and that the generated ROS can be suppressed by pretreatment with the NADPH oxidase (Nox) inhibitor diphenylene iodonium. In addition, transfection with LPA{sub 1} and LPA{sub 3} siRNA efficiently blocked LPA-induced ROS production, suggesting that both receptors are involved in this pathway. Using specific inhibitors and siRNA, phospholipase C (PLC) and protein kinase C (PKC) were also suggested to participate in LPA-induced ROS generation. Overall, we demonstrated that LPA induces ROS generation in PC-3 prostate cancer cells and this is mediated through the PLC/PKC/Nox pathway.

  20. Disulfiram induces copper-dependent stimulation of reactive oxygen species and activation of the extrinsic apoptotic pathway in melanoma.

    PubMed

    Morrison, Brian W; Doudican, Nicole A; Patel, Kirtesh R; Orlow, Seth J

    2010-02-01

    Melanoma is the most aggressive and deadly form of skin cancer. The current standard of care produces response rates of less than 20%, underscoring the critical need for identification of new effective, nontoxic therapies. Disulfiram (DSF) was identified using a drug screen as one of the several compounds that preferentially decreased proliferation in multiple melanoma subtypes compared with benign melanocytes. DSF, a member of the dithiocarbamate family, is a copper (Cu) chelator, and Cu has been shown previously to enhance DSF-mediated growth inhibition and apoptosis in cancer cells. Here, we report that in the presence of free Cu, DSF inhibits cellular proliferation and induces apoptosis in a panel of cell lines representing primary and metastatic nodular and superficial spreading melanoma. Both decreased cellular proliferation and increased apoptosis were seen at 50-500 nmol/l DSF concentrations that are achievable through oral dosing of the medication. In the presence of Cu, DSF caused activation of the extrinsic pathway of apoptosis as measured by caspase-8 cleavage. The addition of Z-IETD-FMK, a selective caspase-8 inhibitor, was protective against DSF-Cu-induced apoptosis. Production of reactive oxygen species (ROS) in response to DSF-Cu treatment preceded the induction of apoptosis. Both ROS production and apoptosis were prevented by coincubation of N-acetyl cysteine, a free radical scavenger. Our study shows that DSF might be used to target both nodular and superficial spreading melanoma through ROS production and activation of the extrinsic pathway of apoptosis.

  1. Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP-1 activation.

    PubMed

    Zou, W; Yan, M; Xu, W; Huo, H; Sun, L; Zheng, Z; Liu, X

    2001-06-15

    Reactive oxygen species (ROS) are supposed to play an important role in hypoxia- and ischemia/reperfusion-mediated neuronal injury with the characteristics of apoptosis. There are many reports showing that cobalt chloride (CoCl(2)) could mimic the hypoxic responses in some aspects including production of ROS in cultured cells. The cytotoxicity of CoCl(2) and its molecular mechanisms have yet to be elucidated. We report that CoCl(2) triggered neuronal PC12 cells apoptosis in a dose- and time-dependent manner. Apoptosis was demonstrated by morphological changes and DNA fragmentation, and was dependent on macromolecular synthesis. Apoptosis was also confirmed by the decrease of the expression of Bcl-X(L). To our knowledge, this is the first documentation of the apoptotic induction of CoCl(2) on PC12 cells. Furthermore, ROS production in PC12 cells was increased during CoCl(2) treatment. Antioxidants, which could inhibit ROS production, significantly blocked CoCl(2)-induced apoptosis, suggesting that apoptosis is mediated by ROS production. We also observed a significant increase of the DNA-binding activity of AP-1 in response to CoCl(2) and this increase was blocked by antioxidants, showing that CoCl(2)-induced apoptosis is accompanied by ROS-activated AP-1. CoCl(2)-treated PC12 cells may serve as an in vitro model for studies of molecular mechanisms in ROS-linked neuronal disorders.

  2. Reactive oxygen species activate a Ca2+-dependent cell death pathway in the unicellular organism Trypanosoma brucei brucei.

    PubMed

    Ridgley, E L; Xiong, Z H; Ruben, L

    1999-05-15

    Here we examine a cell death process induced by reactive oxygen species (ROS) in the haemoflagellate Trypanosoma brucei brucei. Ca2+ distribution in cellular compartments was measured with stable transformants expressing aequorin targeted to the cytosol, nucleus or mitochondrion. Within 1.5 h of ROS production, mitochondrial Ca2+ transport was impaired and the Ca2+ barrier between the nuclear envelope and cytosol was disrupted. Consequently the mitochondrion did not accumulate Ca2+ efficiently in response to an extracellular stimulus, and excess Ca2+ accumulated in the nucleus. The terminal transferase deoxytidyl uridine end labelling assay revealed that, 5 h after treatment with ROS, extensive fragmentation of nuclear DNA occurred in over 90% of the cells. Permeability changes in the plasma membrane did not occur until an additional 2 h had elapsed. The intracellular Ca2+ buffer, EGTA acetoxymethyl ester, prevented DNA fragmentation and prolonged the onset of changes in cell permeability. Despite some similarities to apoptosis, nuclease activation was not a consequence of caspase 3, caspase 1, calpain, serine protease, cysteine protease or proteasome activity. Moreover, trypanosomes expressing mouse Bcl-2 were not protected from ROS even though protection from mitochondrial dysfunction and ROS have been reported for mammalian cells. Overall, these results demonstrate that Ca2+ pathways can induce pathology in trypanosomes, although the specific proteins involved might be distinct from those in metazoans.

  3. A Novel Nontoxic Inhibitor of the Activation of NADPH Oxidase Reduces Reactive Oxygen Species Production in Mouse LungS⃞

    PubMed Central

    Lee, Intae; Dodia, Chandra; Chatterjee, Shampa; Zagorski, John; Mesaros, Clementina; Blair, Ian A.; Feinstein, Sheldon I.; Jain, Mahendra

    2013-01-01

    1-Hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33) is a fluorinated phospholipid analog that inhibits the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6). Prdx6 PLA2 activity is required for activation of NADPH oxidase 2 and subsequent generation of reactive oxygen species (ROS). In vitro, MJ33 inhibited agonist-stimulated production of ROS by the isolated perfused mouse lung, lung microvascular endothelial cells, and polymorphonuclear leukocytes. MJ33 (0.02–0.5 µmol MJ33/kg body weight) in mixed unilamellar liposomes was administered to C57BL/6 mice by either intratracheal (i.t.) or i.v. routes. Lung MJ33 content, measured by liquid chromatography/mass spectroscopy, showed uptake of 67–87% of the injected dose for i.t. and 23–42% for i.v. administration at 4 hours postinjection. PLA2 activity of lung homogenates was markedly inhibited (>85%) at 4 hours postadministration. Both MJ33 content and PLA2 activity gradually returned to near control levels over the subsequent 24–72 hours. Mice treated with MJ33 at 12.5–25 µmol/kg did not show changes (compared with control) in clinical symptomatology, body weight, hematocrit, and histology of lung, liver, and kidney during a 30- to 50-day observation period. Thus, the toxic dose of MJ33 was >25 µmol/kg, whereas the PLA2 inhibitory dose was approximately 0.02 µmol/kg, indicating a high margin of safety. MJ33 administered to mice prior to lung isolation markedly reduced ROS production and tissue lipid and protein oxidation during ischemia followed by reperfusion. Thus, MJ33 could be useful as a therapeutic agent to prevent ROS-mediated tissue injury associated with lung inflammation or in harvested lungs prior to transplantation. PMID:23475902

  4. Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species

    PubMed Central

    Zhao, Ling; Xie, Fei; Wang, Ting-ting; Liu, Meng-yu; Li, Jia-la; Shang, Lei; Deng, Zi-xuan; Zhao, Peng-xiang; Ma, Xue-mei

    2015-01-01

    Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF), one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA) level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH) level, and superoxide dismutase (SOD) and catalase (CAT) activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC) incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases. PMID:26257840

  5. Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes.

    PubMed

    Nedelcu, Aurora M; Marcu, Oana; Michod, Richard E

    2004-08-07

    Organisms are constantly subjected to factors that can alter the cellular redox balance and result in the formation of a series of highly reactive molecules known as reactive oxygen species (ROS). As ROS can be damaging to biological structures, cells evolved a series of mechanisms (e.g. cell-cycle arrest, programmed cell death) to respond to high levels of ROS (i.e. oxidative stress). Recently, we presented evidence that in a facultatively sexual lineage--the multicellular green alga Volvox carteri--sex is an additional response to increased levels of stress, and probably ROS and DNA damage. Here we show that, in V. carteri, (i) sex is triggered by an approximately twofold increase in the level of cellular ROS (induced either by the natural sex-inducing stress, namely heat, or by blocking the mitochondrial electron transport chain with antimycin A), and (ii) ROS are responsible for the activation of sex genes. As most types of stress result in the overproduction of ROS, we believe that our findings will prove to extend to other facultatively sexual lineages, which could be indicative of the ancestral role of sex as an adaptive response to stress and ROS-induced DNA damage.

  6. Norepinephrine causes epigenetic repression of PKCε gene in rodent hearts by activating Nox1-dependent reactive oxygen species production.

    PubMed

    Xiong, Fuxia; Xiao, Daliao; Zhang, Lubo

    2012-07-01

    Heart disease is the leading cause of death in the United States. Recent studies demonstrate that fetal programming of PKCε gene repression results in ischemia-sensitive phenotype in the heart. The present study tests the hypothesis that increased norepinephrine causes epigenetic repression of PKCε gene in the heart via Nox1-dependent reactive oxygen species (ROS) production. Prolonged norepinephrine treatment increased ROS production in fetal rat hearts and embryonic ventricular myocyte H9c2 cells via a selective increase in Nox1 expression. Norepinephrine-induced ROS resulted in an increase in PKCε promoter methylation at Egr-1 and Sp-1 binding sites, leading to PKCε gene repression. N-acetylcysteine, diphenyleneiodonium, and apocynin blocked norepinephrine-induced ROS production and the promoter methylation, and also restored PKCε mRNA and protein to control levels in vivo in fetal hearts and in vitro in embryonic myocyte cells. Accordingly, norepinephrine-induced ROS production, promoter methylation, and PKCε gene repression were completely abrogated by knockdown of Nox1 in cardiomyocytes. These findings provide evidence of a novel interaction between elevated norepinephrine and epigenetic repression of PKCε gene in the heart mediated by Nox1-dependent oxidative stress and suggest new insights of molecular mechanisms linking the heightened sympathetic activity to aberrant cardioprotection and increased ischemic vulnerability in the heart.

  7. Influence of surface oxygenated groups on the formation of active Cu species and the catalytic activity of Cu/AC catalyst for the synthesis of dimethyl carbonate

    NASA Astrophysics Data System (ADS)

    Zhang, Guoqiang; Li, Zhong; Zheng, Huayan; Hao, Zhiqiang; Wang, Xia; Wang, Jiajun

    2016-12-01

    Activated carbon (AC) supported Cu catalysts are employed to study the influence of surface oxygenated groups on the formation of active Cu species and the catalytic activity of Cu/AC catalyst for oxidative carbonylation of methanol to dimethyl carbonate (DMC). The AC supports are thermal treated under different temperatures in order to adjust the levels of surface oxygenated groups. The AC supports are characterized by BET, TPD-MS and XRD, and the Cu/AC catalysts are characterized by BET, XRD, TEM, XPS, AAS, CH3OH-TPD and N2O chemisorption. The results show that as the treatment temperature is below 800 °C, the BET surface area of the corresponding AC supports are nearly unchanged and close to that of the original AC (1529.6 m2/g). But as the thermal treatment temperature is elevated from 1000 to 1600 °C, the BET surface area of AC supports gradually decreases from 1407.6 to 972.2 m2/g. After loading of Cu, the BET surface area of copper catalysts is in the range of 834.4 to 1545.3 m2/g, which is slightly less than that of the respective supports. When AC is thermal treated at 400 and 600 °C, the unstable carboxylic acid and anhydrides groups are selectively removed, which has weakened the mobility and agglomeration of Cu species during the calcination process, and thus improve the Cu species dispersion over AC support. But as the treatment temperature is elevated from 600 °C to 1200 °C, the Cu species dispersion begins to decline suggesting further removal of stable surface oxygenated groups is unfavorable for Cu species dispersion. Moreover, higher thermal treatment temperature (above 1200 °C) promotes the graphitization degree of AC and leds to the decrease of Cu loading on AC support. Meanwhile, the removal of surface oxygenated groups by thermal treatment is conducive to the formation of more π-sites, and thus promote the reduction of Cu2+ to Cu+ and Cu0 as active centers. The specific surface area of (Cu+ + Cu0) is improved by thermal treatment of AC

  8. Humic acid effect on catalase activity and the generation of reactive oxygen species in corn (Zea mays).

    PubMed

    Cordeiro, Flávio Couto; Santa-Catarina, Claudete; Silveira, Vanildo; de Souza, Sonia Regina

    2011-01-01

    Humic acids (HAs) have positive effects on plant physiology, but the molecular mechanisms underlying these events are only partially understood. The induction of root growth and emission of lateral roots (LRs) promoted by exogenous auxin is a natural phenomenon. Exogenous auxins are also associated with HA. Gas nitric oxide (NO) is a secondary messenger produced endogenously in plants. It is associated with metabolic events dependent on auxin. With the application of auxin, NO production is significantly increased, resulting in positive effects on plant physiology. Thus it is possible to evaluate the beneficial effects of the application of HA as an effect of auxin. To investigate the effects of HA the parameters of root growth, Zea mays was studied by evaluating the application of 3 mM C L⁻¹ of HA extracted from Oxisol and 100 µM SNP (sodium nitroprusside) and the NO donor, subject to two N-NO₃⁻, high dose (5.0 mM N-NO₃⁻) and low dose (5.0 mM N-NO₃⁻). Treatments with HA and NO were positively increased, regardless of the N-NO₃⁻ taken, as assessed by fresh weight and dry root, issue of LRs. The effects were more pronounced in the treatment with a lower dose of N-NO₃⁻. Detection of reactive oxygen species (ROS) in vivo and catalase activity were evaluated; these tests were associated with root growth. Under application of the bioactive substances tested, detection of ROS and catalase activity increased, especially in treatments with lower doses of N-NO₃⁻. The results of this experiment indicate that the effects of HA are dependent on ROS generation, which act as a messenger that induces root growth and the emission of LRs.

  9. 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

  10. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    SciTech Connect

    Chen Baoying; Lam, Karen S.L.; Wang Yu; Wu Donghai; Lam, Michael C.; Shen Jiangang; Wong Laiching; Hoo, Ruby L.C.; Zhang Jialiang; Xu Aimin . E-mail: amxu@hkucc.hku.hk

    2006-03-10

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H{sub 2}O{sub 2})-induced dysregulation of adiponectin and PAI-1 production. H{sub 2}O{sub 2} treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) and CCAAT/enhancer binding protein (C/EBP{alpha}), but had no effect on HIF-1{alpha}, whereas hypoxia stabilized HIF-1{alpha} and decreased expression of C/EBP{alpha}, but not PPAR{gamma}. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.

  11. Role of oxygen active species in the photocatalytic degradation of phenol using polymer sensitized TiO2 under visible light irradiation.

    PubMed

    Zhang, Dongdong; Qiu, Rongliang; Song, Lin; Eric, Brewer; Mo, Yueqi; Huang, Xiongfei

    2009-04-30

    The role of dissolved oxygen, and of active species generated by photo-induced reactions with oxygen, in the photocatalytic degradation of phenol was investigated using polymer [poly-(fluorene-co-thiophene) with thiophene content of 30%, so-called PFT30] sensitized TiO2 (PFT30/TiO2) under visible light irradiation. The photoluminescent (PL) quantum yield of PFT30/TiO2 was about 30% of that of PFT30/Al(2)O(3), proving that electron transfer took place between the polymer and TiO2. The result that photocatalytic degradation of phenol was almost stopped when the solution was saturated with N(2) proved the importance of O(2). Addition of NaN(3), an effective quencher of singlet oxygen ((1)O(2)), caused about a 40% decrease in the phenol degradation ratio. Addition of alcohols caused about a 60% decrease in the phenol photodegradation ratio, indicating that the hydroxyl radicals (OH), whose presence was confirmed by electron spin resonance (ESR) spectroscopy, was the predominant active species in aqueous solution. In anhydrous solution, singlet oxygen ((1)O(2)) was the predominant species. These results indicate that oxygen plays a very important role in the photocatalytic degradation of phenol.

  12. Increased level of reactive oxygen species persuades postovulatory aging-mediated spontaneous egg activation in rat eggs cultured in vitro.

    PubMed

    Premkumar, Karuppanan V; Chaube, Shail K

    2016-05-01

    The present study was aimed to find out whether increased level of reactive oxygen species (ROS) particularity hydrogen peroxide (H2O2) could persuade postovulatory aging-mediated abortive spontaneous egg activation (SEA) in rat eggs cultured in vitro. For this purpose, ROS and H2O2 levels, mitochondria distribution and its membrane potential, p286-CaMK-II, Emi2, Thr-161 phophorylated cyclin-dependent protein kinase1 (Cdk1) as well as cyclin B1 levels, in vitro effects of 3-tert-butyl-4 hydroxy anisole (BHA), pentoxifylline and dibutyryl-adenosine 3',5'-cyclic monophosphate (db-cAMP) were analyzed during postovulatory aging-induced abortive SEA in vitro. Data of the present study suggest that postovulatory aging increased H2O2 levels, disturbed mitochondrial distribution pattern and mitochondrial membrane potential (MMP) in eggs. There was an significant increase of p286-CaMK-II level, while Emi2 level reduced significantly during egg aging in vitro. The reduced Emi2 level was associated with decreased Thr-161 phosphorylated cyclin-dependent kinase-1 (Cdk1) as well as cyclin B1 level in aged eggs that underwent abortive SEA. Further, supplementation of pentoxifylline, db-cAMP, and BHA protected postovulatory aging-mediated abortive SEA in concentration-dependent manner. These data suggest that postovulatory aging increased H2O2 levels, reduced MMP, and increased p286-CaMK-II. The increased p286-CaMK-II was associated with reduced Emi2 level and maturation-promoting factor levels during postovulatory aging-mediated abortive SEA. Drugs that elevate cAMP directly or indirectly and BHA protected postovulatory aging-mediated abortive SEA possibly by reducing ROS level in rat eggs cultured in vitro.

  13. Green tea extract protects endothelial progenitor cells from oxidative insult through reduction of intracellular reactive oxygen species activity

    PubMed Central

    Widowati, Wahyu; Widyanto, Rahma Micho; Husin, Winsa; Ratnawati, Hana; Laksmitawati, Dian Ratih; Setiawan, Bambang; Nugrahenny, Dian; Bachtiar, Indra

    2014-01-01

    Objective(s): Many studies have reported that tea consumption decreases cardiovascular risk, but the mechanisms remain unclear. Green tea is known to have potent antioxidant and free radical scavenging activities. This study aimed to investigate whether green tea extract (GTE) can protect endothelial progenitors cells (EPCs) against oxidative stress through antioxidant mechanisms. Materials and Methods: Mononuclear cells (MNCs) were isolated from peripheral blood by density gradient centrifugation with Ficoll. The cells were then plated on fibronectin-coated culture dishes. After 7 days of culture, EPCs were characterized as adherent cells double positive for DiI-ac-LDL uptake and lectin binding. EPCs were further identified by assessing the expression of CD34/45, CD133, and KDR. EPCs were then treated with hydrogen peroxide (H2O2) at doses of 50, 100, 200 µM and incubated with or without GTE (25 µg/ml). The intracellular reactive oxygen species (ROS) levels were detected by flow cytometry using a 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescent probe. Results: GTE ameliorated the cell viability of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 25.47, 22.52, and 11.96% higher than controls, respectively. GTE also decreased the intracellular ROS levels of EPCs induced by H2O2 at doses of 50, 100, 200 µM for about 84.24, 92.27, and 93.72% compared to controls, respectively. Conclusion: GTE improves cell viability by reducing the intracellular ROS accumulation in H2O2-induced EPCs. PMID:25691948

  14. 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.

  15. Structure of dihydrochalcones and related derivatives and their scavenging and antioxidant activity against oxygen and nitrogen radical species.

    PubMed

    Bentes, Alexandre L A; Borges, Rosivaldo S; Monteiro, Waldinei R; de Macedo, Luiz G M; Alves, Cláudio N

    2011-02-21

    Quantum mechanical calculations at B3LYP/6-31G** level of theory were employed to obtain energy (E), ionization potential (IP), bond dissociation enthalpy (O-H BDE) and stabilization energies (DE(iso)) in order to infer the scavenging activity of dihydrochalcones (DHC) and structurally related compounds. Spin density calculations were also performed for the proposed antioxidant activity mechanism of 2,4,6-trihydroxyacetophenone (2,4,6-THA). The unpaired electron formed by the hydrogen abstraction from the phenolic hydroxyl group of 2,4,6-THA is localized on the phenolic oxygen at 2, 6, and 4 positions, the C₃ and C₆ carbon atoms at ortho positions, and the C₅ carbon atom at para position. The lowest phenolic oxygen contribution corresponded to the highest scavenging activity value. It was found that antioxidant activity depends on the presence of a hydroxyl at the C2 and C4 positions and that there is a correlation between IP and O-H BDE and peroxynitrite scavenging activity and lipid peroxidation. These results identified the pharmacophore group for DHC.

  16. Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to induce mitochondrial cytochrome c release and apoptosis in response to malonate.

    PubMed

    Gomez-Lazaro, M; Galindo, M F; Melero-Fernandez de Mera, R M; Fernandez-Gómez, F J; Concannon, C G; Segura, M F; Comella, J X; Prehn, J H M; Jordan, J

    2007-03-01

    Malonate, an inhibitor of mitochondrial complex II, is a widely used toxin to study neurodegeneration in Huntington's disease and ischemic stroke. We have shown previously that malonate increased reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells, leading to oxidative stress, cytochrome c release, and apoptotic cell death. Expression of a green fluorescent protein-Bax fusion protein in SH-SY5Y neuroblastoma cells demonstrated a Bax redistribution from the cytosol to mitochondria after 12 to 24 h of malonate treatment that coincided with mitochondrial potential collapse and chromatin condensation. Inhibition of Bax translocation using furosemide, as well as Bax gene deletion, afforded significant protection against malonate-induced apoptosis. Further experiments revealed that malonate induced a prominent increase in the level of activated p38 mitogen-activated protein (MAP) kinase and that treatment with the p38 MAP kinase inhibitor SKF86002 potently blocked malonate-induced Bax translocation and apoptosis. Treatment with vitamin E diminished ROS production, reduced the activation status of p38 MAP kinase, inhibited Bax translocation, and protected against malonate-induced apoptosis. Our data suggest that malonate-induced ROS production and subsequent p38 MAP kinase activation mediates the activation of the pro-apoptotic Bax protein to induce mitochondrial membrane permeabilization and neuronal apoptosis.

  17. 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.

  18. Bamboo Vinegar Decreases Inflammatory Mediator Expression and NLRP3 Inflammasome Activation by Inhibiting Reactive Oxygen Species Generation and Protein Kinase C-α/δ Activation

    PubMed Central

    Ka, Shuk-Man; Chen, Ann; Tasi, Yu-Ling; Liu, May-Lan; Chiu, Yi-Chich; Hua, Kuo-Feng

    2013-01-01

    Bamboo vinegar (BV), a natural liquid derived from the condensation produced during bamboo charcoal production, has been used in agriculture and as a food additive, but its application to immune modulation has not been reported. Here, we demonstrated that BV has anti-inflammatory activities both in vitro and in vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide levels in, and interleukin-6 secretion by, lipopolysaccharide-activated macrophages without affecting tumor necrosis factor-α secretion and cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV involved decreased reactive oxygen species production and protein kinase C-α/δ activation. Furthermore, creosol (2-methoxy-4-methylphenol) was indentified as the major anti-inflammatory compound in BV. Impaired cytokine expression and NLR family, pyrin domain-containing 3 (NLRP3) inflammasome activation was seen in mice treated with creosol. These findings provide insights into how BV regulates inflammation and suggest that it may be a new source for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation- and NLRP3 inflammasome-related diseases, including metabolic syndrome. PMID:24124509

  19. 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.

  20. Induction of Apoptosis by [8]-shogaol via Reactive Oxygen Species Generation, Glutathione Depletion and Caspase Activation in Human Leukemia Cells

    PubMed Central

    Shieh, Po-Chuen; Chen, Yi-Own; Kuo, Daih-Huang; Chen, Fu-An; Tsai, Mei-Ling; Chang, Ing-Shing; Wu, Hou; Sang, Shengmin; Ho, Chi-Tang; Pan, Min-Hsiung

    2010-01-01

    Ginger, the rhizome of Zingiber officinale, is a traditional medicine with carminative effect, anti-nausea, anti-inflammatory, and anti-carcinogenic properties. This study examined the growth inhibitory effects of [8]-shogaol, one of pungent phenolic compounds in ginger, on human leukemia HL-60 cells. It demonstrated that [8]-shogaol was able to induce apoptosis in a time- and concentration-dependent manner. Treatment with [8]-shogaol caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 and procaspase-3 processing. Taken together, these results suggest for the first time that ROS production and depletion of the glutathione that committed to [8]-shogaol-induced apoptosis in HL-60 cells. PMID:20163181

  1. Growth, toxin production, active oxygen species and catalase activity of Microcystis aeruginosa (Cyanophyceae) exposed to temperature stress.

    PubMed

    Giannuzzi, Leda; Krock, Bernd; Minaglia, Melina Celeste Crettaz; Rosso, Lorena; Houghton, Christian; Sedan, Daniela; Malanga, Gabriela; Espinosa, Mariela; Andrinolo, Darío; Hernando, Marcelo

    2016-11-01

    Microcystis are known for their potential ability to synthesize toxins, mainly microcystins (MCs). In order to evaluate the effects of temperature on chlorophyll a (Chl a), growth, physiological responses and toxin production of a native Microcystis aeruginosa, we exposed the cells to low (23°C) and high (29°C) temperature in addition to a 26°C control treatment. Exponential growth rate was significantly higher at 29°C compared to 23°C and control, reaching 0.43, 0.32 and 0.33day(-)(1) respectively. In addition, there was a delay of the start of exponential growth at 23°C. However, the intracellular concentration of Chl a decreased significantly due to temperature change. A significant increase in intracellular ROS was observed in coincidence with the activation of enzymatic antioxidant catalase (CAT) during the first two days of exposure to 23° and 29°C in comparison to the control experiment, decreasing thereafter to nearly initial values. Five MCs were determined by LC-MS/MS analysis. In the experiments, the highest MC concentration, 205fg [Leu(1)] MC-LR.cell(-1) expressed as MC-LR equivalent was measured in the beginning of the experiment and subsequently declined to 160fg.cell(-1) on day 2 and 70fg.cell(-1) on day 4 in cells exposed to 29°C. The same trend was observed for all other MCs except for the least abundant MC-LR which showed a continuous increase during exposure time. Our results suggest a high ability of M. aeruginosa to perceive ROS and to rapidly initiate antioxidant defenses with a differential response on MC production.

  2. 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.

  3. MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo.

    PubMed

    Mattox, Taylor A; Young, Martin E; Rubel, Carrie E; Spaniel, Carolyn; Rodríguez, Jessica E; Grevengoed, Trisha J; Gautel, Mathias; Xu, Zhelong; Anderson, Ethan J; Willis, Monte S

    2014-06-01

    MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1's role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1-/- mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. However, total oxygen consumption was decreased [corrected]. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1-/- hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2's regulation of mitochondrial function.

  4. MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

    PubMed Central

    Mattox, Taylor A.; Young, Martin E.; Rubel, Carrie E.; Spaniel, Carolyn; Rodríguez, Jessica E.; Grevengoed, Trisha J.; Gautel, Mathias; Xu, Zhelong; Anderson, Ethan J.; Willis, Monte S.

    2014-01-01

    MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased alpha-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose or oleate oxidation; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function. PMID:24733503

  5. Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water

    PubMed Central

    Hamasaki, Takeki; Harada, Gakuro; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro; Fugetsu, Bunshi; Gong, Wei; Sakata, Ichiro; Shirahata, Sanetaka

    2017-01-01

    Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles. PMID:28182635

  6. Electrochemically reduced water exerts superior reactive oxygen species scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water.

    PubMed

    Hamasaki, Takeki; Harada, Gakuro; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro; Fugetsu, Bunshi; Gong, Wei; Sakata, Ichiro; Shirahata, Sanetaka

    2017-01-01

    Electrochemically reduced water (ERW) is produced near a cathode during electrolysis and exhibits an alkaline pH, contains richly dissolved hydrogen, and contains a small amount of platinum nanoparticles. ERW has reactive oxygen species (ROS)-scavenging activity and recent studies demonstrated that hydrogen-dissolved water exhibits ROS-scavenging activity. Thus, the antioxidative capacity of ERW is postulated to be dependent on the presence of hydrogen levels; however, there is no report verifying the role of dissolved hydrogen in ERW. In this report, we clarify whether the responsive factor for antioxidative activity in ERW is dissolved hydrogen. The intracellular ROS scavenging activity of ERW and hydrogen-dissolved water was tested by both fluorescent stain method and immuno spin trapping assay. We confirm that ERW possessed electrolysis intensity-dependent intracellular ROS-scavenging activity, and ERW exerts significantly superior ROS-scavenging activity in HT1080 cells than the equivalent level of hydrogen-dissolved water. ERW retained its ROS-scavenging activity after removal of dissolved hydrogen, but lost its activity when autoclaved. An oxygen radical absorbance capacity assay, the 2,2-diphenyl-1-picrylhydrazyl assay and chemiluminescence assay could not detect radical-scavenging activity in both ERW and hydrogen-dissolved water. These results indicate that ERW contains electrolysis-dependent hydrogen and an additional antioxidative factor predicted to be platinum nanoparticles.

  7. Gestational hypoxia increases reactive oxygen species and inhibits steroid hormone-mediated upregulation of Ca(2+)-activated K(+) channel function in uterine arteries.

    PubMed

    Zhu, Ronghui; Huang, Xiaohui; Hu, Xiang-Qun; Xiao, DaLiao; Zhang, Lubo

    2014-08-01

    Gestational hypoxia inhibits steroid hormone-induced upregulation of Ca(2+)-activated K(+) (KCa) channel activities in uterine arteries. We tested the hypothesis that increased reactive oxygen species play an important role in hypoxia-mediated inhibition of KCa channel activities. Uterine arteries were isolated from nonpregnant (nonpregnant uterine artery) and near-term (≈142-145 day) pregnant (pregnant uterine artery) sheep maintained at either sea level or high altitude (3820 m, Pao2: 60 mm Hg) for 110 days. In pregnant uterine arteries, hypoxia significantly decreased large conductance channel opener NS1619- and small conductance channel opener NS309-induced relaxations, which were partially restored by reactive oxygen species inhibitor N-acetylcysteine (NAC). NAC significantly increased large conductance KCa but not small conductance KCa current densities in uterine arterial smooth muscle cells in pregnant animals acclimatized to high altitude. The NAC-sensitive component of small conductance KCa-induced relaxations was diminished in endothelium-denuded arteries. In nonpregnant uterine arteries, NS1619- and NS309-induced relaxations were diminished compared with those in pregnant uterine arteries. Treatment of nonpregnant uterine arteries with 17β-estradiol and progesterone for 48 hours increased small conductance KCa type 3 protein abundance and NS1619- and NS309-induced relaxations, which were inhibited by hypoxia. This hypoxia-mediated inhibition was reversed by NAC. Consistently, steroid hormone treatment had no significant effects on large conductance KCa current density in nonpregnant uterine arteries of hypoxic animals in the absence of NAC but significantly increased it in the presence of NAC. These results suggest an important role of hypoxia-mediated reactive oxygen species in negatively regulating steroid hormone-mediated upregulation of KCa channel activity and adaptation of uterine vascular reactivity in pregnancy, which may contribute to the

  8. 2-amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production --a microarray analysis study.

    PubMed

    Liang, Rong Mei; Yong, Xiao Lan; Jiang, Yun Ping; Tan, Yong Hong; Dai, Bao Di; Wang, Shi Hua; Hu, Ting Ting; Chen, Xi; Li, Nan; Dong, Zhao Hui; Huang, Xiao Chun; Chen, Jun; Cao, Yong Bing; Jiang, Yuan Ying

    2011-04-01

    Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.

  9. Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression.

    PubMed

    do Vale, Gabriel T; Gonzaga, Natália A; Simplicio, Janaina A; Tirapelli, Carlos R

    2017-03-15

    We studied whether the β1-adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O2(-)) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H2O2) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Nox1, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxo1), c-Src, p47(phox) or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) Cδ and Rac1. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKCδ and Rac1, which are important activators of NADPH oxidase.

  10. Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

    SciTech Connect

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do

    2012-03-01

    Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H{sub 2}O{sub 2}) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H{sub 2}O{sub 2} increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells

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

    PubMed

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

    2015-10-13

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

  12. 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

  13. Caspase-3 activation downstream from reactive oxygen species in heat-induced apoptosis of pancreatic carcinoma cells carrying a mutant p53 gene.

    PubMed

    Kobayashi, D; Sasaki, M; Watanabe, N

    2001-04-01

    In the present study we investigated the intracellular signaling pathway leading to p53-independent activation of caspase-3 during heat-induced apoptosis of pancreatic carcinoma cells. Induction of mutant p53 protein, but not p21/WAF-1, was observed after heat treatment of both heat-resistant (PANC-1) and heat-sensitive (MIAPaCa-2) cells. A specific inhibitor of caspase-3 (Ac-DMQD-CHO) caused 84% and 92% inhibition of apoptosis in MIAPaCa-2 and PANC-1 cells, respectively. Caspase-3 mRNA expression was increased in both cell lines after heat treatment. Further, heat-induced caspase-3 activity detected by fluorogenic assay in MIAPaCa-2 cells was almost completely inhibited by addition of the antioxidant N-acetyl-L-cysteine. In contrast, Ac-DMQD-CHO had no inhibitory effect on amounts of reactive oxygen species in heat-treated MIAPaCa-2 cells. These results suggest a possible pathway by which reactive oxygen species lead to caspase-3 activation to cause heat-induced death of pancreatic carcinoma cells carrying mutant p53.

  14. 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

  15. [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.

  16. Copper-catalyzed activation of molecular oxygen for oxidative destruction of acetaminophen: The mechanism and superoxide-mediated cycling of copper species.

    PubMed

    Zhang, Yunfei; Fan, Jinhong; Yang, Bo; Huang, Wutao; Ma, Luming

    2017-01-01

    In this study, the commercial zero-valent copper (ZVC) was investigated to activate the molecular oxygen (O2) for the degradation of acetaminophen (ACT). 50 mg/L ACT could be completely decomposed within 4 h in the ZVC/air system at initial pH 3.0. The H2O2, hydroxyl radical (OH) and superoxide anion radical (O2(-)) were identified as the main reactive oxygen species (ROSs) generated in the above reaction; however, only OH caused the decomposition and mineralization of ACT in the copper-catalyzed O2 activation process. In addition, the in-situ generated Cu(+) from ZVC dissolution not only activated O2 to produce H2O2, but also initiated the decomposition of H2O2 to generate OH. Meanwhile, the H2O2 could also be partly decomposed into O2(-), which served as a mediator for copper cycling by reduction of Cu(2+) to Cu(+) in the ZVC/air system. Therefore, OH could be continuously generated; and then ACT was effectively degraded. Additionally, the effect of solution pH and the dosage of ZVC were also investigated. As a result, this study indicated the key behavior of the O2(-) during Cu-catalyzed activation of O2, which further improved the understanding of O2 activation mechanism by zero-valent metals.

  17. Superoxide Dismutases and Reactive Oxygen Species

    SciTech Connect

    Cabelli, D.E.

    2011-01-01

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

  18. 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

  19. Formation and Detoxification of Reactive Oxygen Species

    ERIC Educational Resources Information Center

    Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

    2004-01-01

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

  20. Insight into the Mechanism of Antibacterial Activity of ZnO: Surface Defects Mediated Reactive Oxygen Species Even in the Dark.

    PubMed

    Lakshmi Prasanna, V; Vijayaraghavan, Rajagopalan

    2015-08-25

    A systematic and complete antibacterial study on well-designed and well-characterized microparticle (micro), nanoparticle (nano), and capped nano ZnO has been carried out in both dark and light conditions with the objective of arriving at the mechanism of the antibacterial activity of ZnO, particularly in the dark. The present systematic study has conclusively proved that reactive oxygen species (ROS) such as (•)OH, (•)O2(-), and H2O2 are significantly produced from aqueous suspension of ZnO even in the dark and are mainly responsible for the activity in the dark up to 17%, rather than Zn(2+) ion leaching as proposed earlier. This work further confirms that surface defects play a major role in the production of ROS both in the presence and absence of light. In the dark, superoxide ((•)O2(-)) radical mediated ROS generation through singly ionized oxygen vacancy is proposed for the first time, and it is confirmed by EPR and scavenger studies. ROS such as (•)O2(-), H2O2, and (•)OH have been estimated by UV-visible spectroscopy using nitro blue tetrazolium (NBT), KMnO4 titrations, and fluorescence spectroscopy, respectively. These are correlated to the antibacterial activity of ZnO in the dark and light. The activity is found to be highest for nano ZnO and least for micro ZnO, with capped ZnO between the two, highlighting the important role of surface defects in generation of ROS. The surface charge density of ZnO in dark and light has been estimated for the first time to the best of our knowledge, and it can influence antibacterial activity. Our work proposes a new mechanism mediated by superoxide species, for antibacterial activity of ZnO especially in the dark.

  1. Increased reactive oxygen species production down-regulates peroxisome proliferator-activated alpha pathway in C2C12 skeletal muscle cells.

    PubMed

    Cabrero, Agatha; Alegret, Marta; Sanchez, Rosa M; Adzet, Tomas; Laguna, Juan C; Carrera, Manuel Vazquez

    2002-03-22

    Generation of reactive oxygen species may contribute to the pathogenesis of diseases involving intracellular lipid accumulation. To explore the mechanisms leading to these pathologies we tested the effects of etomoxir, an inhibitor of carnitine palmitoyltransferase I which contains a fatty acid-derived structure, in C2C12 skeletal muscle cells. Etomoxir treatment for 24 h resulted in a down-regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA expression, achieving an 87% reduction at 80 microm etomoxir. The mRNA levels of most of the PPARalpha target genes studied were reduced at 100 microm etomoxir. By using several inhibitors of de novo ceramide synthesis and C(2)-ceramide we showed that they were not involved in the effects of etomoxir. Interestingly, the addition of triacsin C, a potent inhibitor of acyl-CoA synthetase, to etomoxir-treated C2C12 skeletal muscle cells did not prevent the down-regulation in PPARalpha mRNA levels, suggesting that the active form of the drug, etomoxir-CoA, was not involved. Given that saturated fatty acids may generate reactive oxygen species (ROS), we determined whether the addition of etomoxir resulted in ROS generation. Etomoxir increased ROS production and the activity of the well known redox transcription factor NF-kappaB. In the presence of the pyrrolidine dithiocarbamate, a potent antioxidant and inhibitor of NF-kappaB activity, etomoxir did not down-regulate PPARalpha mRNA in C2C12 skeletal muscle cells. These results indicate that ROS generation and NF-kappaB activation are responsible for the down-regulation of PPARalpha and may provide a new mechanism by which intracellular lipid accumulation occurs in skeletal muscle cells.

  2. 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

  3. Sunlight-Triggered Nanoparticle Synergy: Teamwork of Reactive Oxygen Species and Nitric Oxide Released from Mesoporous Organosilica with Advanced Antibacterial Activity.

    PubMed

    Gehring, Julia; Trepka, Bastian; Klinkenberg, Nele; Bronner, Hannah; Schleheck, David; Polarz, Sebastian

    2016-03-09

    Colonization of surfaces by microorganisms is an urging problem. In combination with the increasing antibiotic resistance of pathogenic bacteria, severe infections are reported more frequently in medical settings. Therefore, there is a large demand to explore innovative surface coatings that provide intrinsic and highly effective antibacterial activity. Materials containing silver nanoparticles have been developed in the past for this purpose, but this solution has come into criticism due to various disadvantages like notable toxicity against higher organisms, the high price, and low abundance of silver. Here, we introduce a new, sunlight-mediated organosilica nanoparticle (NP) system based on silver-free antibacterial activity. The simultaneous release of nitric oxide (NO) in combination with singlet oxygen and superoxide radicals (O2(•-)) as reactive oxygen species (ROS) leads to the emergence of highly reactive peroxynitrite molecules with significantly enhanced biocidal activity. This special cooperative effect can only be realized, if the ROS-producing moieties and the functional entities releasing NO are spatially separated from each other. In one type of particle, Rose Bengal as an efficient singlet oxygen ((1)O2) producer was covalently bound to SH functionalities applying thiol-ene click chemistry. "Charging" the second type of particles with NO was realized by quantitatively transferring the thiol groups into S-nitrosothiol functionalities. We probed the oxidation power of ROS-NP alone and in combination with NO-NP using sunlight as a trigger. The high antibacterial efficiency of dual-action nanoparticles was demonstrated using disinfection assays with the pathogenic bacterium Pseudomonas aeruginosa.

  4. Effect of scavengers of active oxygen species on cell damage caused in CHO-K1 cells by phenylhydroquinone, an o-phenylphenol metabolite.

    PubMed

    Tayama, S; Nakagawa, Y

    1994-07-01

    Phenylhydroquinone (PHQ), a metabolite of o-phenylphenol (OPP), is easily autoxidized to phenylbenzoquinone (PBQ) via the semiquinone (phenylsemiquinone, PSQ) with concomitant production of superoxide anion radicals (O2-.). We have used scavengers of active oxygen species to examine whether or not O2-. produced during oxidation of PHQ is related to cell damage in CHO-K1 cells. PHQ at 10 micrograms/ml (3-h treatment) induced sister-chromatid exchange (SCE), endoreduplication (ERD) and cell-cycle delay in CHO-K1 cells. These effects were inhibited by catalase (280 U/ml), a scavenger of hydrogen peroxide (H2O2), as well as by the reductants, ascorbate (3 mM) and GSH (1 mM). Mannitol (50 mM), a scavenger of hydroxyl radical (OH.), was ineffective and superoxide dismutase (SOD, 150 U/ml), a scavenger of O2-., or SOD plus catalase rather intensified the toxicity as did aminotriazole (20 mM), an inhibitor of catalase. Analyses of incubation solutions by HPLC showed that the extent of cell damage is correlated with PHQ loss; catalase suppressed PHQ loss, whereas SOD promoted it. The correlation was more clearly seen in the time courses of cell death and PHQ loss during incubation of PHQ with each of the scavengers of active oxygen species. These results show that neither O2-. nor OH. participates in the cell damage, but rather H2O2 generated via dismutation of O2-. may participate, probably by accelerating the autoxidation of PHQ and thus causing an increase in the production of toxic intermediates. In fact, conversion of PHQ to PBQ, a reactive product, was demonstrated during incubation with PHQ in phosphate-buffered saline by following the changes in UV-visible spectra of PHQ. Inclusion of H2O2 (0.2 or 1 mM) in the incubation mixture accelerated the PHQ loss. The present results can be explained in terms of the autoxidation mechanism of hydroquinone proposed by O'Brien (1991). Different from the results in the absence of S9 mix, the cell damage induced by 50 micrograms

  5. Ca2+-dependent generation of mitochondrial reactive oxygen species serves as a signal for poly(ADP-ribose) polymerase-1 activation during glutamate excitotoxicity

    PubMed Central

    Duan, Yuntao; Gross, Robert A; Sheu, Shey-Shing

    2007-01-01

    Mitochondrial Ca2+ uptake and poly(ADP-ribose) polymerase-1 (PARP-1) activation are both required for glutamate-induced excitotoxic neuronal death. Since activation of the glutamate receptors can induce increased levels of reactive oxygen species (ROS), we investigated the relationship of mitochondrial Ca2+ uptake and ROS generation, and the possibility that ROS increase is a required signal for PARP-1 activation in cultured striatal neurons. Based on the spatial profile of NMDA-induced ROS generation, we found that only mitochondria showed a significant ROS increase within 30 min after NMDA receptor activation. This ROS increase was inhibited by the mitochondrial complex inhibitors rotenone and oligomycin, but not by the cytosolic phospholipase A2 or xanthine oxidase inhibitors. Mitochondrial ROS generation was also inhibited by both removal of Ca2+ from extracellular medium and blockage of mitochondrial Ca2+ uptake by either a mitochondrial uncoupler or a Ca2+ uniporter inhibitor. Furthermore, both DNA damage and PARP-1 activation induced by NMDA treatment was inhibited by blocking mitochondrial Ca2+ uptake or by antioxidants. Our results demonstrate that ROS production during the early stage of acute excitotoxicity derives primarily from mitochondria and is Ca2+-dependent. More importantly, the increase of mitochondrial ROS serves as a signal for PARP-1 activation, suggesting that concomitant mitochondrial Ca2+ uptake and PARP-1 activation constitute a unified mechanism for excitotoxic neuronal death. PMID:17947304

  6. 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

  7. 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

  8. Catha edulis Extract Induces H9c2 Cell Apoptosis by Increasing Reactive Oxygen Species Generation and Activation of Mitochondrial Proteins

    PubMed Central

    Mohan, Syam; Abdelwahab, Siddig Ibrahim; Hobani, Yahya Hasan; Syam, Suvitha; Al-Zubairi, Adel S.; Al-Sanousi, Rashad; Oraiby, Magbool Essa

    2016-01-01

    Background: Catha edulis (Khat) is an evergreen shrub or small tree, traditionally used by various peoples of the Arabian Peninsula and Africa as an integral component of the socioeconomic traditions. It is believed that the psychostimulant nature and toxic nature of khat is primarily due to the presence of cathinone and cathine respectively. Studies have shown that khat chewing is closely associated with cardiac complications, especially myocardial infarction. Hence in this study, we exposed cathine-rich khat extract in a cardiomyoblast H9c2 (2-1) cell line to check the cell death mechanism. Materials and Methods: Extraction of Catha edulis leaves was done and the presence of cathine was confirmed with LC-MS-MS. The anti-proliferative activity was assayed using MTT and apoptosis detection by acridine orange/propidium iodide assay. The expression of Bcl-2 and Bax protein and caspase-3/7 expression were analyzed. The level of reactive oxygen species generation was also evaluated. Results: The khat extract showed an IC50 value of 86.5 μg/ml at 48 hours treatment. We have observed significant early apoptosis events by intervened acridine orange within the fragmented DNA with bright green fluorescence upon treatment. The Bcl-2 expression in the treatment with IC50 concentration of khat extract for 24, 48 and 72 hours of incubation significantly decreased with increase in bax level. The increased activation of caspase-3/7 was significantly observed upon treatment together with significant increase of ROS was detected at 24 and 48 hours treatment. Conclusion: Collectively, our results provide insight into the mechanisms by which Catha edulis leaves mediate cell death in cardiomyocytes. SUMMARY Catha edulis (Khat) is an evergreen psychotropic shrub or small treeExtraction of khat leaves was done and the presence of cathine was confirmed with liquid chromatography-mass spectrometry-mass spectrometryThe khat extract showed an IC50 value of 86.5 μg/ml at 48 h treatment in

  9. Reactive Oxygen Species-Dependent c-Fos/Activator Protein 1 Induction Upregulates Heme Oxygenase-1 Expression by Bradykinin in Brain Astrocytes.

    PubMed

    Hsieh, Hsi-Lung; Wang, Hui-Hsin; Wu, Cheng-Ying; Yang, Chuen-Mao

    2010-12-15

    Heme oxygenase-1 (HO-1) plays a crucial role in tissue pathological changes such as brain injuries. Our previous studies have demonstrated that bradykinin (BK) induces the expression of several inflammatory proteins, including matrix metalloproteinase-9 and COX-2, via mitogen-activated protein kinases and nuclear factor-κB (NF-κB) in rat brain astrocytes (RBA-1). However, the molecular mechanisms underlying BK-induced HO-1 expression in RBA-1 cells remain poorly defined. Here we demonstrated that BK induced HO-1 expression and enzymatic activity via a B(2) BK receptor-activated reactive oxygen species (ROS)-dependent signaling pathway. NADPH oxidase (Nox)-dependent ROS generation led to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun-N-terminal kinase (JNK) and then activated the downstream molecules NF-κB and c-Jun, respectively. The c-Fos, an activator protein 1 (AP-1) subunit, was upregulated by activation of NF-κB and c-Jun, which bound to HO-1 promoter and thereby turned on transcription of HO-1 gene. The rat HO-1 promoter containing a putative AP-1 cis-binding site was identified as a crucial domain linking to BK action. Taken together, these results suggested that in RBA-1 cells, activation of ERK/NF-κB and JNK/c-Jun cascades by a Nox/ROS-dependent event enhancing c-Fos/AP-1 activity is essential for HO-1 upregulation and activation induced by BK. Moreover, ROS-dependent NF-E2-related factor 2 activation also contributes to HO-1 induction by BK in astrocytes.

  10. Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species.

    PubMed

    Goyal, Parag; Weissmann, Norbert; Grimminger, Friedrich; Hegel, Cornelia; Bader, Lucius; Rose, Frank; Fink, Ludger; Ghofrani, Hossein A; Schermuly, Ralph T; Schmidt, Harald H H W; Seeger, Werner; Hänze, Jörg

    2004-05-15

    Hypoxia sensing and related signaling events, including activation of hypoxia-inducible factor 1 (HIF-1), represent key features in cell physiology and lung function. Using cultured A549 cells, we investigated the role of NAD(P)H oxidase 1 (Nox1), suggested to be a subunit of a low-output NAD(P)H oxidase complex, in hypoxia signaling. Nox1 expression was detected on both the mRNA and protein levels. Upregulation of Nox1 mRNA and protein occurred during hypoxia, accompanied by enhanced reactive oxygen species (ROS) generation. A549 cells, which were transfected with a Nox1 expression vector, revealed an increase in ROS generation accompanied by activation of HIF-1-dependent target gene expression (heme oxygenase 1 mRNA, hypoxia-responsive-element reporter gene activity). In A549 cells stably overexpressing Nox1, accumulation of HIF-1alpha in normoxia and an additional increase in hypoxia were noted. Interference with ROS metabolism by the flavoprotein inhibitor diphenylene iodonium (DPI) and catalase inhibited HIF-1 induction. This suggests that H2O2 links Nox1 and HIF-1 activation. We conclude that hypoxic upregulation of Nox1 and subsequently augmented ROS generation may activate HIF-1-dependent pathways.

  11. Co-occurring increases of calcium and organellar reactive oxygen species determine differential activation of antioxidant and defense enzymes in Ulva compressa (Chlorophyta) exposed to copper excess.

    PubMed

    Gonzalez, Alberto; Vera, Jeannette; Castro, Jorge; Dennett, Geraldine; Mellado, Macarena; Morales, Bernardo; Correa, Juan A; Moenne, Alejandra

    2010-10-01

    In order to analyse copper-induced calcium release and (reactive oxygen species) ROS accumulation and their role in antioxidant and defense enzymes activation, the marine alga Ulva compressa was exposed to 10 µM copper for 7 d. The level of calcium, extracellular hydrogen peroxide (eHP), intracellular hydrogen peroxide (iHP) and superoxide anions (SA) as well as the activities of ascorbate peroxidase (AP), glutathione reductase (GR), glutathione-S-transferase (GST), phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX) were determined. Calcium release showed a triphasic pattern with peaks at 2, 3 and 12 h. The second peak was coincident with increases in eHP and iHP and the third peak with the second increase of iHP. A delayed wave of SA occurred after day 3 and was not accompanied by calcium release. The accumulation of iHP and SA was mainly inhibited by organellar electron transport chains inhibitors (OETCI), whereas calcium release was inhibited by ryanodine. AP activation ceased almost completely after the use of OETCI. On the other hand, GR and GST activities were partially inhibited, whereas defense enzymes were not inhibited. In contrast, PAL and LOX were inhibited by ryanodine, whereas AP was not inhibited. Thus, copper stress induces calcium release and organellar ROS accumulation that determine the differential activation of antioxidant and defense enzymes.

  12. Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy.

    PubMed

    Min, Kisuk; Kwon, Oh-Sung; Smuder, Ashley J; Wiggs, Michael P; Sollanek, Kurt J; Christou, Demetra D; Yoo, Jeung-Ki; Hwang, Moon-Hyon; Szeto, Hazel H; Kavazis, Andreas N; Powers, Scott K

    2015-04-15

    Although doxorubicin (DOX) is a highly effective anti-tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX-mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX-induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial-targeted anti-oxidant to prevent DOX-induced increases in mitochondrial ROS emission, whereas a highly-selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX-mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX-induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX-induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX-induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX-induced myopathy in both cardiac and skeletal muscle fibres.

  13. Synergistic anticandidal activity of pure polyphenol curcumin I in combination with azoles and polyenes generates reactive oxygen species leading to apoptosis.

    PubMed

    Sharma, Monika; Manoharlal, Raman; Negi, Arvind Singh; Prasad, Rajendra

    2010-08-01

    We have shown previously that pure polyphenol curcumin I (CUR-I) shows antifungal activity against Candida species. By employing the chequerboard method, filter disc and time-kill assays, in the present study we demonstrate that CUR-I at non-antifungal concentration interacts synergistically with azoles and polyenes. For this, pure polyphenol CUR-I was tested for synergy with five azole and two polyene drugs - fluconazole (FLC), miconazole, ketoconazole (KTC), itraconazole (ITR), voriconazole (VRC), nystatin (NYS) and amphotericin B (AMB) - against 21 clinical isolates of Candida albicans with reduced antifungal sensitivity, as well as a drug-sensitive laboratory strain. Notably, there was a 10-35-fold drop in the MIC(80) values of the drugs when CUR-I was used in combination with azoles and polyenes, with fractional inhibitory concentration index (FICI) values ranging between 0.09 and 0.5. Interestingly, the synergistic effect of CUR-I with FLC and AMB was associated with the accumulation of reactive oxygen species, which could be reversed by the addition of an antioxidant such as ascorbic acid. Furthermore, the combination of CUR-I and FLC/AMB triggered apoptosis that could also be reversed by ascorbic acid. We provide the first evidence that pure CUR-I in combination with azoles and polyenes represents a novel therapeutic strategy to improve the activity of common antifungals.

  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. Artemisinin induces A549 cell apoptosis dominantly via a reactive oxygen species-mediated amplification activation loop among caspase-9, -8 and -3.

    PubMed

    Gao, Weijie; Xiao, Fenglian; Wang, Xiaoping; Chen, Tongsheng

    2013-10-01

    This report is designed to explore the roles of caspase-8, -9 and -3 in artemisinin (ARTE)-induced apoptosis in non-small cell lung cancer cells (A549 cells). ARTE induced reactive oxygen species (ROS)-mediated apoptosis in dose- and time-dependent fashion. Although ARTE treatment did not induce Bid cleavage and significant loss of mitochondrial membrane potential, it induced release of Smac and AIF but not cytochrome c from mitochondria, and silencing of Bak but not Bax significantly prevented ARTE-induced cytotoxicity. Moreover, ARTE treatment induced ROS-dependent activation of caspase-9, -8 and -3. Of the utmost importance, silencing or inhibiting any one of caspase-8, -9 and -3 almost completely prevented ARTE-induced activation of all the three caspases and remarkably abrogated the cytotoxicity of ARTE, suggesting that ARTE triggered an amplification activation loop among caspase-9, -8 and -3. Collectively, our data demonstrate that ARTE induces a ROS-mediated amplification activation loop among caspase-9, -8 and -3 to dominantly mediate the apoptosis of A549 cells.

  16. 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.

  17. New cell-based assay indicates dependence of antioxidant biological activity on the origin of reactive oxygen species.

    PubMed

    Dimitrov, Martin D; Pesheva, Margarita G; Venkov, Pencho V

    2013-05-08

    The mobility of the Ty1 transposon in Saccharomyces cerevisiae was found to vary proportionally with the level of ROS generated in cells, which provides the possibility to determine antioxidant activity by changes in a cellular process instead of using chemical reactions. The study of propolis, royal jelly, and honey with the newly developed Ty1antiROS test reveals an inverse exponential dependence of antioxidant activity on increased concentrations. This dependence can be transformed to proportional by changing the source of ROS: instead of cell-produced to applied as hydrogen peroxide. The different test responses are not due to excess of added hydrogen peroxide, as evidenced by the exponential dependence found by usage of yap1Δ tester cells accumulating cell-generated ROS. Results indicate that the activity of antioxidants to oxidative radicals depends on the origin of ROS, and this activity is elevated for cell-generated ROS compared to ROS added as reagents in the assay.

  18. Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming

    PubMed Central

    Liu, Xiuting; Zhang, Xin; Ding, Yang; Zhou, Wei; Tao, Lei; Lu, Ping; Wang, Yajing

    2017-01-01

    Abstract Aims: The NLRP3 inflammasome is a multiprotein complex that protects hosts against a variety of pathogens. However, the molecular mechanisms of modulating NLRP3 inflammasome activation, especially at the priming step, are still poorly understood. This study was designed to elucidate the negative regulation of nuclear factor E2-related factor-2 (Nrf2) on the activation of NLRP3 inflammasome. Results: We reported that Nrf2 activation inhibited NLRP3 expression, caspase-1 cleavage, and subsequent IL-1β generation. Compared with normal cells, Nrf2-deficient cells showed upregulated cleaved caspase-1, which were attributed to the increased transcription of NLRP3 caused by excess reactive oxygen species (ROS). Furthermore, priming of the NLRP3 inflammasome was sensitive to the exogenous ROS levels induced by H2O2 or rotenone. Combined with adenosine triphosphate, rotenone triggered higher activity of the NLRP3 inflammasome compared with lipopolysaccharide, suggesting that ROS promoted the priming step. In addition, Nrf2-induced NQO1 was involved in the inhibition of the NLRP3 inflammasome. In an in vivo alum-induced peritonitis mouse model, Nrf2 activation suppressed typical IL-1 signaling-dependent inflammation, whereas Nrf2−/− mice exhibited a significant increase in the recruitment of immune cell and the generation of IL-1β compared with wild-type mice. Innovation: We elucidated the effects and possible mechanisms of Nrf2 activation-induced NQO1 expression on NLRP3 inflammasome inactivation and established a novel regulatory role of the Nrf2 pathway in ROS-induced NLRP3 priming. Conclusions: We demonstrated Nrf2 negatively regulating NLRP3 inflammasome activity by inhibiting the priming step and suggested that Nrf2 could be a potential target for some uncontrolled inflammasome activation-associated diseases. Antioxid. Redox Signal. 26, 28–43. PMID:27308893

  19. 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.

  20. Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

    PubMed Central

    Sanchez-Alavez, Manuel; Bortell, Nikki; Galmozzi, Andrea; Conti, Bruno; Marcondes, Maria Cecilia G.

    2014-01-01

    Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation of peripheral thermogenic sites such as the Brown Adipose Tissue (BAT). In a previous study we found that the anti-oxidant N-acetyl cysteine (NAC) can prevent the high increase in temperature in a mouse model of Meth-hyperthermia. Here, we have further explored the ability of NAC to modulate Meth-induced hyperthermia in correlation with changes in BAT. We found that NAC treatment in controls causes hypothermia, and, when administered prior or upon the onset of Meth-induced hyperthermia, can ameliorate the temperature increase and preserve mitochondrial numbers and integrity, without affecting locomotor activity. This was different from Dantrolene, which decreased motor activity without affecting temperature. The effects of NAC were seen in spite of its inability to recover the decrease of mitochondrial superoxide induced in BAT by Meth. In addition, NAC did not prevent the Meth-induced decrease of BAT glutathione. Treatment with S-adenosyl-L-methionine, which improves glutathione activity, had an effect in ameliorating Meth-induced hyperthermia, but also modulated motor activity. This suggests a role for the remaining glutathione for controlling temperature. However, the mechanism by which NAC operates is independent of glutathione levels in BAT and specific to temperature. Our results show that, in spite of the absence of a clear mechanism of action, NAC is a pharmacological tool to examine the dissociation between Meth-induced hyperthermia and motor activity, and a drug of potential utility in treating the hyperthermia associated with Meth-abuse. PMID:26346736

  1. Irradiation with UV-C inhibits TNF-α-dependent activation of the NF-κB pathway in a mechanism potentially mediated by reactive oxygen species.

    PubMed

    Szoltysek, Katarzyna; Walaszczyk, Anna; Janus, Patryk; Kimmel, Marek; Widlak, Piotr

    2017-01-01

    Pathways depending on the NF-κB transcription factor are essential components of cellular response to stress. Plethora of stimuli modulating NF-κB includes inflammatory signals, ultraviolet radiation (UV) and reactive oxygen species (ROS), yet interference between different factors affecting NF-κB remains relatively understudied. Here, we aim to characterize the influence of UV radiation on TNF-α-induced activity of the NF-κB pathway. We document inhibition of TNF-α-induced activation of NF-κB and subsequent suppression of NF-κB-regulated genes in cells exposed to UV-C several hours before TNF-α stimulation. Accumulation of ROS and subsequent activation of NRF2, p53, AP-1 and NF-κB-dependent pathways, with downstream activation of antioxidant mechanisms (e.g., SOD2 and HMOX1 expression), is observed in the UV-treated cells. Moreover, NF-κB inhibition is not observed if generation of UV-induced ROS is suppressed by chemical antioxidants. It is noteworthy that stimulation with TNF-α also generates a wave of ROS, which is suppressed in cells pre-treated by UV. We postulate that irradiation with UV-C activates antioxidant mechanisms, which in turn affect ROS-mediated activation of NF-κB by TNF-α. Considering a potential cross talk between p53 and NF-κB, we additionally compare observed effects in p53-proficient and p53-deficient cells and find the UV-mediated suppression of TNF-α-activated NF-κB in both types of cells.

  2. Antifungal Activity of Plasmacytoid Dendritic Cells against Cryptococcus neoformans In Vitro Requires Expression of Dectin-3 (CLEC4D) and Reactive Oxygen Species

    PubMed Central

    Hole, Camaron R.; Leopold Wager, Chrissy M.; Mendiola, Andrew S.; Wozniak, Karen L.; Campuzano, Althea; Lin, Xin

    2016-01-01

    Conventional dendritic cells (cDCs) are critical for protection against pulmonary infection with the opportunistic fungal pathogen Cryptococcus neoformans; however, the role of plasmacytoid dendritic cells (pDCs) is unknown. We show for the first time that murine pDCs have direct activity against C. neoformans via reactive oxygen species (ROS), a mechanism different from that employed to control Aspergillus fumigatus infections. The anticryptococcal activity of murine pDCs is independent of opsonization but appears to require the C-type lectin receptor Dectin-3, a receptor not previously evaluated during cryptococcal infections. Human pDCs can also inhibit cryptococcal growth by a mechanism similar to that of murine pDCs. Experimental pulmonary infection of mice with a C. neoformans strain that induces protective immunity demonstrated that recruitment of pDCs to the lungs is CXCR3 dependent. Taken together, our results show that pDCs inhibit C. neoformans growth in vitro via the production of ROS and that Dectin-3 is required for optimal growth-inhibitory activity. PMID:27324480

  3. Epoxyeicosatrienoic Acids Attenuate Reactive Oxygen Species Level, Mitochondrial Dysfunction, Caspase Activation, and Apoptosis in Carcinoma Cells Treated with Arsenic TrioxideS⃞

    PubMed Central

    Liu, Liu; Chen, Chen; Gong, Wei; Li, Yuanjing; Edin, Matthew L.; Zeldin, Darryl C.

    2011-01-01

    Epoxyeicosatrienoic acids (EETs) and the cytochrome P450 epoxygenase CYP2J2 promote tumorogenesis in vivo and in vitro via direct stimulation of tumor cell growth and inhibition of tumor cell apoptosis. Herein, we describe a novel mechanism of inhibition of tumor cell apoptosis by EETs. In Tca-8113 cancer cells, the antileukemia drug arsenic trioxide (ATO) led to the generation of reactive oxygen species (ROS), impaired mitochondrial function, and induced apoptosis. 11,12-EET pretreatment increased expression of the antioxidant enzymes superoxide dismutase and catalase and inhibited ATO-induced apoptosis. 11,12-EET also prevented the ATO-induced activation of p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, caspase-3, and caspase-9. Therefore, 11,12-EET-pretreatment attenuated the ROS generation, loss of mitochondrial function, and caspase activation observed after ATO treatment. Moreover, the CYP2J2-specific inhibitor compound 26 enhanced arsenic cytotoxicity to a clinically relevant concentration of ATO (1–2 μM). Both the thiol-containing antioxidant, N-acetyl-cysteine, and 11,12-EET reversed the synergistic effect of the two agents. Taken together, these data indicate that 11,12-EET inhibits apoptosis induced by ATO through a mechanism that involves induction of antioxidant proteins and attenuation of ROS-mediated mitochondrial dysfunction. PMID:21846841

  4. MIF-driven activation of macrophages induces killing of intracellular Trypanosoma cruzi dependent on endogenous production of tumor necrosis factor, nitric oxide and reactive oxygen species.

    PubMed

    Cutrullis, Romina A; Petray, Patricia B; Corral, Ricardo S

    2017-02-01

    The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is a key player in innate immunity. MIF has been considered critical for controlling acute infection by the protozoan Trypanosoma cruzi, but the underlying mechanisms are poorly understood. Our study aimed to analyze whether MIF could favor microbicidal activity of the macrophage, a site where T. cruzi grows and the initial effector cell against this parasite. Using murine macrophages infected in vitro, we examined the effect of MIF on their parasiticidal ability and attempted to identify inflammatory agents involved in MIF-induced protection. Our findings show that MIF is readily secreted from peritoneal macrophages upon T. cruzi infection. MIF activates both primary and J774 phagocytes boosting the endogenous production of tumor necrosis factor-alpha via mitogen-activated protein kinase p38 signaling, as well as the release of nitric oxide and reactive oxygen species, leading to enhanced pathogen elimination. MIF can also potentiate the effect of interferon-gamma on T. cruzi killing by J774 and mouse peritoneal macrophages, rendering these cells more competent in reducing intracellular parasite burden. The present results unveil a novel innate immune pathway that contributes to host defense and broaden our understanding of the regulation of inflammatory mediators implicated in early parasite containment that is decisive for resistance to T. cruzi infection.

  5. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    PubMed

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation.

  6. Integrin alpha1beta1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation.

    PubMed

    Chen, Xiwu; Abair, Tristin D; Ibanez, Maria R; Su, Yan; Frey, Mark R; Dise, Rebecca S; Polk, D Brent; Singh, Amar B; Harris, Raymond C; Zent, Roy; Pozzi, Ambra

    2007-05-01

    Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin alpha1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by alpha1-null mesangial cells. In the present studies, we describe the mechanism whereby integrin alpha1-null mesangial cells produce excessive ROS. Integrin alpha1-null mesangial cells have constitutively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand-independent increased epidermal growth factor receptor (EGFR) phosphorylation in alpha1-null mesangial cells. Thus, our study demonstrates that integrin alpha1beta1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis.

  7. Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species.

    PubMed

    Zhang, Aifeng; Sheng, Yuqing; Zou, Mingchang

    2017-03-01

    Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis.

  8. 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

  9. Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids.

    PubMed Central

    Malis, C D; Weber, P C; Leaf, A; Bonventre, J V

    1990-01-01

    Experiments were designed to evaluate the susceptibility of mitochondrial membranes enriched with n-3 fatty acids to damage by Ca2+ and reactive oxygen species. Fatty acid content and respiratory function were assessed in renal cortical mitochondria isolated from fish-oil- and beef-tallow-fed rats. Dietary fish oils were readily incorporated into mitochondrial membranes. After exposure to Ca2+ and reactive oxygen species, mitochondria enriched in n-3 fatty acids, and using pyruvate and malate as substrates, had significantly greater changes in state 3 and uncoupled respirations, when compared with mitochondria from rats fed beef tallow. Mitochondrial site 1 (NADH coenzyme Q reductase) activity was reduced to 45 and 85% of control values in fish-oil- and beef-tallow-fed groups, respectively. Exposure to Ca2+ and reactive oxygen species enhance the release of polyunsaturated fatty acids enriched at the sn-2 position of phospholipids from mitochondria of fish-oil-fed rats when compared with similarly treated mitochondria of beef-tallow-fed rats. This release of fatty acids was partially inhibited by dibucaine, the phospholipase A2 inhibitor, which we have previously shown to protect mitochondria against damage associated with Ca2+ and reactive oxygen species. The results indicate that phospholipase A2 is activated in mitochondria exposed to Ca2+ and reactive oxygen species and is responsible, at least in part, for the impairment of respiratory function. Phospholipase A2 activity and mitochondrial damage are enhanced when mitochondrial membranes are enriched with n-3 fatty acids. PMID:2123344

  10. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen.

    PubMed

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper; Arthur, Jonathan W; Graham, Mark E; Lavin, Martin

    2016-03-01

    Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

  11. Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species-mediated ERK activation in HL-60 leukemia cells and xenograft.

    PubMed

    Lee, Wei-Jiunn; Hsiao, Michael; Chang, Junn-Liang; Yang, Shun-Fa; Tseng, Tsui-Hwa; Cheng, Chao-Wen; Chow, Jyh-Ming; Lin, Ke-Hsun; Lin, Yung-Wei; Liu, Chung-Chi; Lee, Liang-Ming; Chien, Ming-Hsien

    2015-07-01

    Quercetin is a plant-derived bioflavonoid that was recently shown to have multiple anticancer activities in various solid tumors. Here, novel molecular mechanisms through which quercetin exerts its anticancer effects in acute myeloid leukemia (AML) cells were investigated. Results from Western blot and flow cytometric assays revealed that quercetin significantly induced caspase-8, caspase-9, and caspase-3 activation, poly ADP-ribose polymerase (PARP) cleavage, and mitochondrial membrane depolarization in HL-60 AML cells. The induction of PARP cleavage by quercetin was also observed in other AML cell lines: THP-1, MV4-11, and U937. Moreover, treatment of HL-60 cells with quercetin induced sustained activation of extracellular signal-regulated kinase (ERK), and inhibition of ERK by an ERK inhibitor significantly abolished quercetin-induced cell apoptosis. MitoSOX red and 2',7'-dichlorofluorescin fluorescence, respectively, showed that mitochondrial superoxide and intracellular peroxide levels were higher in quercetin-treated HL-60 cells compared with the control group. Moreover, both N-acetylcysteine and the superoxide dismutase mimetic, MnTBAP, reversed quercetin-induced intracellular reactive oxygen species production, ERK activation, and subsequent cell death. The in vivo xenograft mice experiments revealed that quercetin significantly reduced tumor growth through inducing intratumoral oxidative stress while activating the ERK pathway and subsequent cell apoptosis in mice with HL-60 tumor xenografts. In conclusions, our results indicated that quercetin induced cell death of HL-60 cells in vitro and in vivo through induction of intracellular oxidative stress following activation of an ERK-mediated apoptosis pathway.

  12. Impact of fungicides on active oxygen species and antioxidant enzymes in spring barley (Hordeum vulgare L.) exposed to ozone.

    PubMed

    Wu, Yue-xuan; von, Tiedemann Andreas

    2002-01-01

    Two modern fungicides, a strobilurin, azoxystrobin (AZO), and a triazole, epoxiconazole (EPO), applied as foliar spray on spring barley (Hordeum vulgare L. cv. Scarlett) 3 days prior to fumigation with injurious doses of ozone (150-250 ppb; 5 days; 7 h/day) induced a 50-60% protection against ozone injury on leaves. Fungicide treatments of barley plants at growth stage (GS) 32 significantly increased the total leaf soluble protein content. Additionally, activities of the antioxidative enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate-peroxidase (APX) and glutathione reductase (GR) were increased by both fungicides at maximal rates of 16, 75, 51 and 144%, respectively. Guiacol-peroxidase (POX) activity was elevated by 50-110% only in AZO treated plants, while this effect was lacking after treatments with EPO. This coincided with elevated levels of hydrogen peroxide (H2O2) only in EPO and not in AZO treated plants. The enhancement of the plant antioxidative system by the two fungicides significantly and considerably reduced the level of superoxide (O2*-) in leaves. Fumigation of barley plants for 4 days with non-injurious ozone doses (120-150 ppb, 7 h/day) markedly and immediately stimulated O2*- accumulation in leaves, while H2O2 was increased only after the third day of fumigation. Therefore, O2*- itself or as precursor of even more toxic oxyradicals appears to be more indicative for ozone-induced leaf damage than H2O2. Ozone also induced significant increases in the activity of antioxidant enzymes (SOD, POX and CAT) after 2 days of fumigation in fungicide untreated plants, while after 4 days of fumigation these enzymes declined to a level lower than in unfumigated plants, due to the oxidative degradation of leaf proteins. This is the first report demonstrating the marked enhancement of plant antioxidative enzymes and the enhanced scavenging of potentially harmful O2*- by fungicides as a mechanism of protecting plants against noxious oxidative stress

  13. Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45.

    PubMed

    Kim, Minjeong; Baek, Heung Soo; Lee, Miri; Park, Hyeonji; Shin, Song Seok; Choi, Dal Woong; Lim, Kyung-Min

    2016-04-01

    Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma.

  14. A Minimal Cysteine Motif Required to Activate the SKOR K+ Channel of Arabidopsis by the Reactive Oxygen Species H2O2*

    PubMed Central

    Garcia-Mata, Carlos; Wang, Jianwen; Gajdanowicz, Pawel; Gonzalez, Wendy; Hills, Adrian; Donald, Naomi; Riedelsberger, Janin; Amtmann, Anna; Dreyer, Ingo; Blatt, Michael R.

    2010-01-01

    Reactive oxygen species (ROS) are essential for development and stress signaling in plants. They contribute to plant defense against pathogens, regulate stomatal transpiration, and influence nutrient uptake and partitioning. Although both Ca2+ and K+ channels of plants are known to be affected, virtually nothing is known of the targets for ROS at a molecular level. Here we report that a single cysteine (Cys) residue within the Kv-like SKOR K+ channel of Arabidopsis thaliana is essential for channel sensitivity to the ROS H2O2. We show that H2O2 rapidly enhanced current amplitude and activation kinetics of heterologously expressed SKOR, and the effects were reversed by the reducing agent dithiothreitol (DTT). Both H2O2 and DTT were active at the outer face of the membrane and current enhancement was strongly dependent on membrane depolarization, consistent with a H2O2-sensitive site on the SKOR protein that is exposed to the outside when the channel is in the open conformation. Cys substitutions identified a single residue, Cys168 located within the S3 α-helix of the voltage sensor complex, to be essential for sensitivity to H2O2. The same Cys residue was a primary determinant for current block by covalent Cys S-methioylation with aqueous methanethiosulfonates. These, and additional data identify Cys168 as a critical target for H2O2, and implicate ROS-mediated control of the K+ channel in regulating mineral nutrient partitioning within the plant. PMID:20605786

  15. Activation of biologically relevant levels of reactive oxygen species by Au/g-C3N4 hybrid nanozyme for bacteria killing and wound disinfection.

    PubMed

    Wang, Zhenzhen; Dong, Kai; Liu, Zhen; Zhang, Yan; Chen, Zhaowei; Sun, Hanjun; Ren, Jinsong; Qu, Xiaogang

    2017-01-01

    As common reactive oxygen species, H2O2 is widely used for bacterial inactivation and wound disinfection. However, the concentrations used are always higher than physiological levels, which frequently result in potential toxicity to healthy tissue and even delay wound healing. Here we report highly efficient nanozyme hybrids that are capable of activating biologically relevant concentrations of H2O2 for defending bacterial infections. The integration of AuNPs with ultrathin graphitic carbon nitride (g-C3N4) provides excellent peroxidase-activity, which can catalyze the decomposition of H2O2 to OH radicals much more efficiently, allowing the use of bio-safety levels of H2O2 for the first time. Furthermore, our system not only exhibits striking bactericidal performance against both DR Gram-negative and DR Gram-positive bacteria, but also shows high efficiency in breaking down the existing DR-biofilms and prevented formation of new biofilms in vitro. More importantly, in vivo experiments indicate that our system could significantly prevent bacterial infections and accelerate the healing rate of wounds.

  16. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    SciTech Connect

    Yun, Hong Shik; Hong, Eun-Hee; Lee, Su-Jae; Baek, Jeong-Hwa; Lee, Chang-Woo; Yim, Ji-Hye; Um, Hong-Duck; Hwang, Sang-Gu

    2013-09-27

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer.

  17. Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species.

    PubMed

    Wei, Chunmei; Xiao, Qing; Kuang, Xingyi; Zhang, Tao; Yang, Zesong; Wang, Li

    2015-11-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and a high risk of progression to acute myeloid leukaemia (AML). Fucoidan, a complex sulphated polysaccharide isolated from the cell wall of brown seaweeds, has recently attracted attention for its multiple biological activities and its potential as a novel candidate for cancer therapy. In the present study, the anti‑cancer activity of fucoidan was investigated in the MDS/AML cell line SKM‑1. Fucoidan inhibited proliferation, induced apoptosis and caused G1-phase arrest of the cell cycle in SKM‑1 cells as determined by a cell counting kit 8 assay and flow cytometry. Furthermore, reverse transcription quantitative polymerase chain reaction and western blot analyses indicated that treatment with fucoidan (100 µg/ml for 48 h) activated Fas and caspase‑8 in SKM‑1 cells, which are critical for the extrinsic apoptotic pathway; furthermore, caspase‑9 was activated via decreases in phosphoinositide-3 kinase/Akt signaling as indicated by reduced levels of phosphorylated Akt, suggesting the involvement of the intrinsic apoptotic pathway. In addition, fucoidan treatment of SKM‑1 cells resulted in the generation of reactive oxygen species (ROS) as determined by staining with dichloro-dihydro-fluorescein diacetate. These results suggested that the mechanisms of the anti‑cancer effects of fucoidan in SKM‑1 are closely associated with cell cycle arrest and apoptotic cell death, which partly attributed to the activation of apoptotic pathways and accumulation of intracellular ROS. Our results demonstrated that Fucoidan inhibits proliferation and induces the apoptosis of SKM‑1 cells, which provides substantial therapeutic potential for MDS treatment.

  18. DNA breakage induced by 1,2,4-benzenetriol: relative contributions of oxygen-derived active species and transition metal ions.

    PubMed

    Li, A S; Bandy, B; Tsang, S; Davison, A J

    2001-05-01

    We report here the relative roles of metals and selected reactive oxygen species in DNA damage by the genotoxic benzene metabolite 1,2,4-benzenetriol, and the interactions of antioxidants in affording protection. 1,2,4-Benzenetriol induces scission in supercoiled phage DNA in neutral aqueous solution with an effective dose (ED(50)) of 6.7 microM for 50% cleavage of 2.05 microg/ml supercoiled PM2 DNA. In decreasing order of effectiveness: catalase (20 U/ml), formate (25 mM), superoxide dismutase (20 U/ml), and mannitol (50 mM) protected, from 85 to 28%. Evidently, H(2)O(2) is the dominant active species, with O(2)(*)(-) and *OH playing subordinate roles. Desferrioxamine or EDTA inhibited DNA breakage by 81-85%, despite accelerating 1,2,4-benzenetriol autoxidation. Consistent with this suggestion of a crucial role for metals, addition of cupric, cuprous, ferric, or ferrous ions enhanced DNA breakage, with copper being more active than iron. Combinations of scavengers protected more effectively than any single scavenger alone, with implications for antioxidants acting in concert in living cells. Synergistic combinations were superoxide dismutase with *OH scavengers, superoxide dismutase with desferrioxamine, and catalase with desferrioxamine. Antagonistic (preemptive) combinations were catalase with superoxide dismutase, desferrioxamine with *OH scavengers, and catalase with *OH scavengers. The most striking aspect of synergism was the extent to which metal chelation (desferrioxamine) acted synergistically with either catalase or superoxide dismutase to provide virtually complete protection. Concluding, 1,2,4-benzenetriol-induced DNA damage occurs mainly by site-specific, Fenton-type mechanisms, involving synergism between several reactive intermediates. Multiple antioxidant actions are needed for effective protection.

  19. 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

  20. Macrophages generate reactive oxygen species in response to minimally oxidized LDL: TLR4- and Syk-dependent activation of Nox2

    PubMed Central

    Bae, Yun Soo; Lee, Jee Hyun; Choi, Soo Ho; Kim, Sunah; Almazan, Felicidad; Witztum, Joseph L.; Miller, Yury I.

    2009-01-01

    Oxidative modification of low-density lipoprotein (LDL) plays a causative role in the development of atherosclerosis. In this study, we demonstrate that minimally oxidized LDL (mmLDL) stimulates intracellular reactive oxygen species (ROS) generation in macrophages through NADPH oxidase 2 (gp91phox/Nox2), which in turn induces production of RANTES and migration of smooth muscle cells. Peritoneal macrophages from gp91phox/Nox2−/− mice or J774 macrophages in which Nox2 was knocked down by siRNA failed to generate ROS in response to mmLDL. Because mmLDL-induced cytoskeletal changes were dependent on TLR4, we analyzed ROS generation in peritoneal macrophages from wild type, TLR4−/−, or MyD88−/− mice and found that mmLDL-mediated ROS was generated in a TLR4-dependent, but MyD88-independent manner. Furthermore, we found that ROS generation required the recruitment and activation of spleen tyrosine kinase (Syk) and that mmLDL also induced PLCγ1 phosphorylation and PKC membrane translocation. Importantly, the PLCγ1 phosphorylation was reduced in J774 cells expressing Syk-specific shRNA. Nox2 modulated mmLDL activation of macrophages by regulating the expression of proinflammatory cytokines IL-1β, IL-6 and RANTES. We showed that purified RANTES was able to stimulate migration of mouse aortic smooth muscle cells (MASMC) and addition of neutralizing antibody against RANTES abolished the migration of MASMC stimulated by mmLDL-stimulated macrophages. These results suggest that mmLDL induces generation of ROS through sequential activation of TLR4, Syk, PLCγ1, PKC, and gp91phox/Nox2 and thereby stimulates expression of proinflammatory cytokines. These data help explain mechanisms by which endogenous ligands, such as mmLDL, can induce TLR4-dependent, proatherogenic activation of macrophages. PMID:19096031

  1. Suppression of reactive oxygen species-mediated ERK and JNK activation sensitizes dihydromyricetin-induced mitochondrial apoptosis in human non-small cell lung cancer.

    PubMed

    Kao, Shang-Jyh; Lee, Wei-Jiunn; Chang, Jer-Hwa; Chow, Jyh-Ming; Chung, Chi-Li; Hung, Wen-Yueh; Chien, Ming-Hsien

    2017-04-01

    Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer with a high mortality rate and still remains a therapeutic challenge. A strategy for targeting NSCLC is to identify agents that are effective against NSCLC cells while sparing normal cells. Dihydromyricetin (DHM) is the major flavonoid component derived from Ampelopsis grossedentata, which has a long history of use in medicine. Herein, the molecular mechanisms by which DHM exerts its anticancer effects against NSCLC cells were investigated. Results from MTS, colony formation, Western blot, flow cytometric, and JC-1 mitochondrial membrane potential assays revealed that DHM showed a selective cytotoxic effect against NSCLC cells (A549 and H1975), but not against normal lung (WI-38) fibroblasts, by inducing apoptosis. DHM-induced cell apoptosis occurred through Bcl-w suppression-mediated mitochondrial membrane depolarization, caspase-9/-7/-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in A549 and H1975 cells. Moreover, treatment of A549 and H1975 cells with DHM induced increase of intracellular peroxide and sustained activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2, and the reactive oxygen species scavenger, N-acetylcysteine (NAC), reversed DHM-induced ERK and JNK activation. Furthermore, treatment of cells with specific inhibitors of ERK and JNK or NAC significantly promoted the DHM-induced activation of caspase-9/-7/-3 and PARP cleavage and also sensitized the antitumorigenic effect of DHM on NSCLC cells. These findings define and support a novel function of DHM of inducing mitochondrion-derived apoptosis in human NSCLC cells, and a combination of DHM with ERK and JNK inhibitors should be a good strategy for preventing NSCLC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1426-1438, 2017.

  2. Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells

    SciTech Connect

    Son, Young-Ok; Hitron, J. Andrew; Wang Xin; Chang Qingshan; Pan Jingju; Zhang Zhuo; Liu Jiankang; Wang Shuxia; Lee, Jeong-Chae; Shi Xianglin

    2010-06-01

    Cr(VI) compounds are known to cause serious toxic and carcinogenic effects. Cr(VI) exposure can lead to a severe damage to the skin, but the mechanisms involved in the Cr(VI)-mediated toxicity in the skin are unclear. The present study examined whether Cr(VI) induces cell death by apoptosis or necrosis using mouse skin epidermal cell line, JB6 Cl41 cells. We also investigated the cellular mechanisms of Cr(VI)-induced cell death. This study showed that Cr(VI) induced apoptotic cell death in a dose-dependent manner, as demonstrated by the appearance of cell shrinkage, the migration of cells into the sub-G1 phase, the increase of Annexin V positively stained cells, and the formation of nuclear DNA ladders. Cr(VI) treatment resulted in the increases of mitochondrial membrane depolarization and caspases activation. Electron spin resonance (ESR) and fluorescence analysis revealed that Cr(VI) increased intracellular levels of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anion radical in dose-dependent manner. Blockage of p53 by si-RNA transfection suppressed mitochondrial changes of Bcl-2 family composition, mitochondrial membrane depolarization, caspase activation and PARP cleavage, leading to the inhibition of Cr(VI)-induced apoptosis. Further, catalase treatment prevented p53 phosphorylation stimulated by Cr(VI) with the concomitant inhibition of caspase activation. These results suggest that Cr(VI) induced a mitochondrial-mediated and caspase-dependent apoptosis in skin epidermal cells through activation of p53, which are mainly mediated by reactive oxidants generated by the chemical.

  3. 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.

  4. 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.

  5. 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.

  6. Silymarin Protects Mouse Liver and Kidney from Thioacetamide Induced Toxicity by Scavenging Reactive Oxygen Species and Activating PI3K-Akt Pathway

    PubMed Central

    Ghosh, Shatadal; Sarkar, Abhijit; Bhattacharyya, Sudip; Sil, Parames C.

    2016-01-01

    Silymarin (SMN) has been shown to possess a wide range of biological and pharmacological effects. Besides, SMN has antioxidant and free radical scavenging activities. Thioacetamide (TAA) is a well-documented liver toxin that requires oxidative bioactivation to elicit its hepatotoxic effect which ultimately modifies amine-lipids and proteins. Our study has been designed in a TAA exposed mouse model to investigate whether SMN could protect TAA-induced oxidative stress mediated hepatic and renal damage. Results suggest that TAA generated reactive oxygen species (ROS), caused oxidative stress and induced apoptosis in the liver and kidney cells via JNK as well as PKC and MAPKs signaling. All these detrimental effects of TAA could, however, be suppressed by SMN which not only scavenged ROS but also induced PI3K-Akt cell survival pathway in the liver and prevented apoptotic pathways in both the organs. Histological studies, collagen staining and DNA fragmentation analysis also supported our results. Combining, we say that SMN possess beneficial role against TAA mediated hepatic and renal pathophysiology. PMID:28018219

  7. In vitro effect of copper chloride exposure on reactive oxygen species generation and respiratory chain complex activities of mitochondria isolated from broiler liver.

    PubMed

    Su, Rongsheng; Wang, Rongmei; Guo, Shining; Cao, Huabin; Pan, Jiaqiang; Li, Chengmei; Shi, Dayou; Tang, Zhaoxin

    2011-12-01

    This study is to examine if Cu(2+) can act directly on mitochondria or indirectly by producing reactive oxygen species (ROS), isolated broiler hepatic mitochondria were exposed to different concentrations of Cu(2+) (10, 30, 50 μM). Respiratory chain complex activities, ROS generation, respiratory control ratio (RCR) and mitochondrial membrane potential were investigated. Dose-dependent inhibition of respiratory chain complexes and induction of ROS were observed, which coincided with decreasing RCR both with glutamate + malate or succinate. Further investigation indicated that the membrane potential determined by rhodamine 123 release decreased after CuCl(2) exposure at 30 and 50 μM. In addition, the effects of the antioxidants NAC (200 μM) and GSH (200 μM) were studied at 50 μM Cu(2+). The results indicate that Cu can induce mitochondrial dysfunction in excessive dose and the effect of Cu(2+) exposure on respiratory chain is not site-specific, and antioxidants can protect the mitochondrial function by reducing the formation of free radicals.

  8. Malonate-induced generation of reactive oxygen species in rat striatum depends on dopamine release but not on NMDA receptor activation.

    PubMed

    Ferger, B; Eberhardt, O; Teismann, P; de Groote, C; Schulz, J B

    1999-09-01

    Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate produces both energy depletion and striatal lesions similar to that seen in cerebral ischemia and Huntington's disease. The mechanisms of neuronal cell death involve secondary excitotoxicity and the generation of reactive oxygen species. Here, we investigated the effects of dopamine on malonate-induced generation of hydroxyl radicals and striatal lesion volumes. Using in vivo microdialysis, we found that malonate induced a 94-fold increase in extracellular striatal dopamine concentrations. This was paralleled by an increase in the generation of hydroxyl radicals. Prior unilateral lesioning of the nigrostriatal dopaminergic pathway by focal injection of 6-hydroxydopamine blocked the malonate-induced increase in dopamine concentrations and the generation of hydroxyl radicals and attenuated the lesion volume. In contrast, the NMDA receptor antagonist MK-801 attenuated malonate-induced lesion volumes but did not block the generation of hydroxyl radicals. Thus, the dopaminergic and glutamatergic pathways are essential in the pathogenesis of malonate-induced striatal lesions. Our results suggest that the malonate-induced release of dopamine but not NMDA receptor activation mediates hydroxyl radical formation.

  9. Effect of Laurus nobilis L. Essential Oil and its Main Components on α-glucosidase and Reactive Oxygen Species Scavenging Activity

    PubMed Central

    Sahin Basak, Serap; Candan, Ferda

    2013-01-01

    The present study was designed to determine the effects of the essential oil of Laurus nobilis L. (Lauraceae) and its three main components on α-glucosidase and reactive oxygen species scavenging activity. The chemical composition of the essential oil from Laurus nobilis L. leaves was analyzed by GC/GC-MS and resulted in the identification of 29 compounds, representing 99.18% of the total oil. 1,8-cineole (68.82%), 1-(S)-α-pinene (6.94%), and R-(+)- limonene (3.04%) were determined to be the main components. The antioxidant features of the essential oil and its three main components were evaluated using inhibition of 2,2-diphenyl-1- picrylhydrazyl, hydroxyl, and superoxide radicals, inhibition of hydrogen peroxide and lipid peroxidation assays. The results show that the DPPH, hydroxyl, and superoxide radical as well as hydrogen peroxide scavenging activities of the essential oil are greater than the positive controls and the three main components of the oil when tested independently. The inhibition of lipid peroxidation by the oil occurred less frequently than with 1,8-cineole and R-(+)- limonene alone, but the effects were more pronounced than those seen with 1-(S)-α-pinene and the positive controls. An α-glucosidase inhibition assay was applied to evaluate the in-vitro antidiabetic activity of the essential oil. IC50-values were obtained for laurel essential oil, 1, 8-cineole, 1-(S)-α-pinene, and R-(+)-limonene: 1.748 μL/mL, 1.118 μL/mL, 1.420 μL/mL and 1.300 μL/mL, respectively. We also found that laurel essential oil and 1, 8-cineole inhibited the α-glucosidase competitively while 1-(S)-α-pinene and R-(+)-limonene were uncompetitive inhibitors. PMID:24250611

  10. Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injury

    SciTech Connect

    Shishido, Tetsuro . E-mail: Tetsuro_Shishido@URMC.Rochester.edu; Nozaki, Naoki; Takahashi, Hiroki; Arimoto, Takanori; Niizeki, Takeshi; Koyama, Yo; Abe, Jun-ichi; Takeishi, Yasuchika; Kubota, Isao

    2006-07-14

    Background: It is now evident that inflammation after vascular injury has significant impact on the restenosis after revascularization procedures such as angioplasty, stenting, and bypass grafting. However, the mechanisms that regulate inflammation and repair after vascular injury are incompletely understood. Here, we report that vascular injury-mediated cytokine expression, reactive oxygen species (ROS) production, as well as subsequent neointimal formation requires Toll-like receptor-2 (TLR-2) mediated signaling pathway in vivo. Methods and results: Vascular injury was induced by cuff-placement around the femoral artery in non-transgenic littermates (NLC) and TLR-2 knockout (TLR-2KO) mice. After cuff-placement in NLC mice, expression of TLR-2 was significantly increased in both smooth muscle medial layer and adventitia. Interestingly, we found that inflammatory genes expression such as tumor necrosis factor-{alpha}, interleukin-1{beta} (IL-1{beta}), IL-6, and monocyte chemoattractant protein-1 were markedly decreased in TLR-2KO mice compared with NLC mice. In addition, ROS production after vascular injury was attenuated in TLR-2KO mice compared with NLC mice. Since we observed the significant role of endogenous TLR-2 activation in regulating inflammatory responses and ROS production after vascular injury, we determined whether inhibition of endogenous TLR-2 activation can inhibit neointimal proliferation after vascular injury. Neointimal hyperplasia was markedly suppressed in TLR-2KO mice compared with WT mice at both 2 and 4 weeks after vascular injury. Conclusions: These findings suggested that endogenous TLR-2 activation might play a central role in the regulation of vascular inflammation as well as subsequent neointimal formation in injured vessels.

  11. Effect of dietary supplementation of vitamin C on growth, reactive oxygen species, and antioxidant enzyme activity of Apostichopus japonicus (Selenka) juveniles exposed to nitrite

    NASA Astrophysics Data System (ADS)

    Luo, Zuoyong; Wang, Baojie; Liu, Mei; Jiang, Keyong; Liu, Mingxing; Wang, Lei

    2014-07-01

    Different amounts of vitamin C were added to diets fed to juveniles (2.5 ± 0.15 g) of sea cucumber Apostichopus japonic u s (Selenka) in an attempt to reduce the stress response of specimens exposed to nitrite stress. A commercial feed was used as the control diet and three experimental diets were made by supplementing 1 000, 1 500, or 2 000 mg vitamin C/kg diet to control diet separately in a 45-day experiment. Sea cucumbers were exposed to three different levels (0.5, 1.0, and 1.5 mg/L) of nitrite stress for 4, 8, and 12 h at four time intervals (0, 15, 30, and 45 d). Growth of the animals was recorded during the experiment. Reactive oxygen species (ROS) (i.e. hydroxyl free radical (-OH), malondialdehyde (MDA) and total antioxidant capacity (T-AOC)) and antioxidant enzyme activities (i.e., superoxide dismutase (SOD) and catalase (CAT)) were measured. Response surface methodology (RSM) was used to analyze the effect of multiple factors on ROS indices and enzyme activities. Weight gain (WG) and special growth rate (SGR) of vitamin C supplementation groups were significantly higher than those of control group ( P < 0.05). The levels of -OH and MDA increased under exposure time extending and nitrite concentration increasing, whereas T-AOC level decreased. SOD and CAT activities increased at 4 h and 8 h and decreased at 12 h. During the days in which the animal consumed experimental diets, the levels of -OH and MDA decreased and that of T-AOC increased. This result suggests that diets containing vitamin C could reduce the nitrite stress response in the animals and increase their antioxidant capacity. The multifactor regression equation of growth performance, ROS indices, and duration of feeding results suggest that vitamin C supplementation of 1 400-2 000 mg/kg diet for 29-35 days could reduce effectively the effects of nitrite exposure.

  12. Resveratrol Sensitizes Acute Myelogenous Leukemia Cells to Histone Deacetylase Inhibitors through Reactive Oxygen Species-Mediated Activation of the Extrinsic Apoptotic PathwayS⃞

    PubMed Central

    Yaseen, Alae; Chen, Shuang; Hock, Stefanie; Rosato, Roberto; Dent, Paul; Dai, Yun

    2012-01-01

    Histone deacetylase inhibitors (HDACIs) activate the prosurvival nuclear factor-κB (NF-κB) pathway by hyperacetylating RelA/p65, whereas the chemopreventive agent resveratrol inhibits NF-κB by activating the class III histone deacetylase Sirt1. Interactions between resveratrol and pan-HDACIs (vorinostat and panobinostat) were examined in human acute myelogenous leukemia (AML) cells. Pharmacologically achievable resveratrol concentrations (25–50 μM) synergistically potentiated HDACI lethality in AML cell lines and primary AML blasts. Resveratrol antagonized RelA acetylation and NF-κB activation in HDACI-treated cells. However, short hairpin RNA Sirt1 knockdown failed to modify HDACI sensitivity, which suggests that factors other than or in addition to Sirt1 activation contribute to resveratrol/HDACI interactions. These interactions were associated with death receptor 5 (DR5) up-regulation and caspase-8 activation, whereas cells expressing dominant-negative caspase-8 were substantially protected from resveratrol/HDACI treatment, which suggests a significant functional role for the extrinsic apoptotic pathway in lethality. Exposure to resveratrol with HDACI induced sustained reactive oxygen species (ROS) generation, which was accompanied by increased levels of DNA double-strand breaks, as reflected in γH2A.X and comet assays. The free radical scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride blocked ROS generation, DR5 up-regulation, caspase-8 activation, DNA damage, and apoptosis, which indicates a primary role for oxidative injury in lethality. Analyses of cell-cycle progression and 5-ethynyl-2′-deoxyuridine incorporation through flow cytometry revealed that resveratrol induced S-phase accumulation; this effect was abrogated by HDACI coadministration, which suggests that cells undergoing DNA synthesis may be particularly vulnerable to HDACI lethality. Collectively, these findings indicate that resveratrol interacts synergistically with HDACIs in

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. 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 ...

  15. Extracellular phosphates enhance activities of voltage-gated proton channels and production of reactive oxygen species in murine osteoclast-like cells.

    PubMed

    Li, Guangshuai; Miura, Katsuyuki; Kuno, Miyuki

    2017-02-01

    Osteoclasts are highly differentiated bone-resorbing cells and play a significant role in bone remodelling. In the resorption pit, inorganic phosphate (Pi) concentrations increase because of degradation of hydroxyapatite. We studied effects of extracellular Pi on voltage-gated H(+) channels in osteoclast-like cells derived from a macrophage cell line (RAW264). Extracellular Pi (1.25-20 mM) increased the H(+) channel currents dose dependently and reversibly. The Pi-induced increases were attenuated by removal of extracellular Na(+) and by phosphonoformic acid, a blocker of Na(+)-dependent Pi transporters. Pi increased the maximal conductance, decreased activation time constant, increased deactivation time constant, and shifted the conductance-voltage relationship to more negative voltages. The most marked change was enhanced gating which was mainly caused by elevation of intracellular Pi levels. The Pi-induced enhanced gating was partially inhibited by protein kinase C (PKC) inhibitors, GF109203X and staurosporine, indicating that PKC-mediated phosphorylation was involved in part. The increase in the maximal conductance was mainly due to accompanying decrease in intracellular pH. These effects of Pi were not affected by intracellular Mg(2+), bafilomycin A1 (V-ATPase inhibitor) and removal of intracellular ATP. Extracellular Pi also upregulated reactive oxygen species (ROS). Diphenyleneiodonium chloride, an inhibitor of NADPH oxidases, decreased ROS production and partially attenuated the enhanced gating. In the cells during later passages where osteoclastogenesis declined, H(+) channel activities and ROS production were both modest. These results suggest that, in osteoclasts, ambient Pi is a common enhancer for H(+) channels and ROS production and that potentiation of H(+) channels may help ROS production.

  16. Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels.

    PubMed

    Nishio, N; Taniguchi, W; Sugimura, Y K; Takiguchi, N; Yamanaka, M; Kiyoyuki, Yasukuni; Yamada, H; Miyazaki, N; Yoshida, M; Nakatsuka, T

    2013-09-05

    Central neuropathic pain (CNP) in the spinal cord, such as chronic pain after spinal cord injury (SCI), is an incurable ailment. However, little is known about the spinal cord mechanisms underlying CNP. Recently, reactive oxygen species (ROS) have been recognized to play an important role in CNP of the spinal cord. However, it is unclear how ROS affect synaptic transmission in the dorsal horn of the spinal cord. To clarify how ROS impact on synaptic transmission, we investigated the effects of ROS on synaptic transmission in rat spinal cord substantia gelatinosa (SG) neurons using whole-cell patch-clamp recordings. Administration of tert-butyl hydroperoxide (t-BOOH), an ROS donor, into the spinal cord markedly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in SG neurons. This t-BOOH-induced enhancement was not suppressed by the Na(+) channel blocker tetrodotoxin. However, in the presence of a non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, t-BOOH did not generate any sEPSCs. Furthermore, in the presence of a transient receptor potential ankyrin 1 (TRPA1) channel antagonist (HC-030031) or a transient receptor potential vanilloid 1 (TRPV1) channel antagonist (capsazepine or AMG9810), the t-BOOH-induced increase in the frequency of sEPSCs was inhibited. These results indicate that ROS enhance the spontaneous release of glutamate from presynaptic terminals onto SG neurons through TRPA1 and TRPV1 channel activation. Excessive activation of these ion channels by ROS may induce central sensitization in the spinal cord and result in chronic pain such as that following SCI.

  17. Arachidonic acid enhances TPA-induced differentiation in human leukemia HL-60 cells via reactive oxygen species-dependent ERK activation.

    PubMed

    Chien, Chih-Chiang; Wu, Ming-Shun; Shen, Shing-Chuan; Yang, Liang-Yo; Wu, Wen-Shin; Chen, Yen-Chou

    2013-04-01

    The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), is a potent stimulator of differentiation in human leukemia cells; however, the effects of arachidonic acid (AA) on TPA-induced differentiation are still unclear. In the present study, we investigated the contribution of AA to TPA-induced differentiation of human leukemia HL-60 cells. We found that treatment of HL-60 cells with TPA resulted in increases in cell attachment and nitroblue tetrazolium (NBT)-positive cells, which were significantly enhanced by the addition of AA. Stimulation of TPA-induced intracellular reactive oxygen species (ROS) production by AA was detected in HL-60 cells via a DCHF-DA analysis, and the addition of the antioxidant, N-acetyl-cysteine (NAC), was able to reduce TPA+AA-induced differentiation in accordance with suppression of intracellular peroxide elevation by TPA+AA. Furthermore, activation of extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) by TPA+AA was identified in HL-60 cells, and the ERK inhibitor, PD98059, but not the JNK inhibitor, SP600125, inhibited TPA+AA-induced NBT-positive cells. Suppression of TPA+AA-induced ERK protein phosphorylation by PD98059 and NAC was detected, and AA enhanced ERK protein phosphorylation by TPA was in HL-60 cells. AA clearly increased TPA-induced HL-60 cell differentiation, as evidenced by a marked increase in CD11b expression, which was inhibited by NAC and PD98059 addition. Eicosapentaenoic acid (EPA) as well as AA showed increased intracellular peroxide production and differentiation of HL-60 cells elicited by TPA. Evidence of AA potentiation of differentiation by TPA in human leukemia cells HL-60 via activation of ROS-dependent ERK protein phosphorylation was first demonstrated herein.

  18. Urinary Sodium Excretion Has Positive Correlation with Activation of Urinary Renin Angiotensin System and Reactive Oxygen Species in Hypertensive Chronic Kidney Disease

    PubMed Central

    Ahn, Shin-Young; Kim, Sejoong; Kim, Dong Ki; Shin, Sung Joon; Lee, Sang Ho; Choi, Bum Soon; Lim, Chun Soo

    2014-01-01

    It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with ≥200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with ≥200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation. PMID:25317016

  19. 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

  20. 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.

  1. Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling.

    PubMed

    Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1(G93A) (ACM-hSOD1(G93A)) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1(G93A), but not ACM-hSOD1(WT), increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1(G93A)-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1(G86R) or TDP43(A315T). We further find that co-application of ACM-SOD1(G93A) with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1(G93A) induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death.

  2. Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling

    PubMed Central

    Rojas, Fabiola; Gonzalez, David; Cortes, Nicole; Ampuero, Estibaliz; Hernández, Diego E.; Fritz, Elsa; Abarzua, Sebastián; Martinez, Alexis; Elorza, Alvaro A.; Alvarez, Alejandra; Court, Felipe; van Zundert, Brigitte

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which pathogenesis and death of motor neurons are triggered by non-cell-autonomous mechanisms. We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1G93A (ACM-hSOD1G93A) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Here we examined the role of mitochondrial structure and physiology and of the activation of c-Abl, a tyrosine kinase that induces apoptosis. We show that ACM-hSOD1G93A, but not ACM-hSOD1WT, increases c-Abl activity in motoneurons, interneurons and glial cells, starting at 60 min; the c-Abl inhibitor STI571 (imatinib) prevents this ACM-hSOD1G93A-mediated motoneuron death. Interestingly, similar results were obtained with ACM derived from astrocytes expressing SOD1G86R or TDP43A315T. We further find that co-application of ACM-SOD1G93A with blockers of Nav channels (spermidine, mexiletine, or riluzole) or anti-oxidants (Trolox, esculetin, or tiron) effectively prevent c-Abl activation and motoneuron death. In addition, ACM-SOD1G93A induces alterations in the morphology of neuronal mitochondria that are related with their membrane depolarization. Finally, we find that blocking the opening of the mitochondrial permeability transition pore with cyclosporine A, or inhibiting mitochondrial calcium uptake with Ru360, reduces ROS production and c-Abl activation. Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. ROS production, mediated at least in part through mitochondrial alterations, trigger c-Abl signaling and lead to motoneuron death. PMID:26106294

  3. mGluR5 stimulating Homer–PIKE formation initiates icariin induced cardiomyogenesis of mouse embryonic stem cells by activating reactive oxygen species

    SciTech Connect

    Zhou, Limin; Huang, Yujie; Zhang, Yingying; Zhao, Qingwei; Zheng, Bei; Lou, Yijia; Zhu, Danyan

    2013-06-10

    Icariin (ICA) has been reported to facilitate cardiac differentiation of mouse embryonic stem (ES) cells; however, the mechanism by which ICA induced cardiomyogenesis has not been fully elucidated yet. Here, an underlying signaling network including metabotropic glutamate receptor 5 (mGluR5), Homer, phosphatidylinositol 3-Kinase Enhancer (PIKE), phosphatidylinositol 3-Kinase (PI3K), reactive oxygen species (ROS) and nuclear factor-kappaB (NF-κB) was investigated in ICA induced cardiomyogenesis. Our results showed that the co-expression of mGluR5 together with α-actinin or Troponin T in embryoid bodies (EBs) treated with ICA was elevated to 10.86% and 9.62%, compared with the case in the control (4.04% and 3.45%, respectively). Exposure of EBs to ICA for 2 h remarkably increased the dimeric form of mGluR5, which was inhibited by small interfering RNA targeting mGluR5 (si-mGluR5). Moreover, the extracellular glutamate concentration in ICA treatment medium was elevated to 28.9±3.5 μM. Furthermore, the activation of mGluR5 by ICA triggered the formation of Homer–PIKE complex and activated PI3K, stimulating ROS generation and NF-κB nuclear translocation. Knockdown of mGluR5 or inhibition of PI3K by LY294002 blocked ICA induced cardiomyogenesis via repressing mGluR5 pathway, reducing ROS and NF-κB activation. These results revealed that the inducible mechanisms of ICA were related to activate mGluR5 pathway. -- Highlights: • ICA increased mGluR5 expression in cardiac differentiation of ES cells. • ICA enhanced the glutamate level and the receptor mGluR5 dimerization, stimulating the formation of Homer–PIKE complex. • Knockdown of mGluR5 or inhibition of PI3K by LY294002 inhibited ICA induced ROS generation and NF-κB nuclear translocation.

  4. Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling

    SciTech Connect

    Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo; Lee, Jeong-Chae; Shi, Xianglin

    2013-09-01

    Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100 nM) for 3 months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. - Highlights: • Chronic exposure to Cr(VI) induces carcinogenic properties in BEAS-2B cells. • ROS play an important role in Cr(VI)-induced tumorigenicity of BEAS-2B cells. • PI3K/AKT/GSK-3β/β-catenin signaling involved in Cr

  5. Non-transferrin bound iron, cytokine activation and intracellular reactive oxygen species generation in hemodialysis patients receiving intravenous iron dextran or iron sucrose.

    PubMed

    Pai, Amy Barton; Conner, Todd; McQuade, Charles R; Olp, Jonathan; Hicks, Paul

    2011-08-01

    Intravenous (IV) iron supplementation is widely used to support erythropoeisis in hemodialysis patients. IV iron products are associated with oxidative stress that has been measured principally by circulating biomarkers such as products of lipid peroxidation. The pro-oxidant effects of IV iron are presumed to be due at least in part, by free or non-transferrin bound iron (NTBI). However, the effects of IV iron on intracellular redox status and downstream effectors is not known. This prospective, crossover study compared cytokine activation, reactive oxygen species generation and oxidative stress after single IV doses of iron sucrose and iron dextran. This was a prospective, open-label, crossover study. Ten patients with end-stage renal disease (ESRD) on hemodialysis and four age and sex-matched healthy were assigned to receive 100 mg of each IV iron product over 5 min in random sequence with a 2 week washout between products. Subjects were fasted and fed a low iron diet in the General Clinical Research Center at the University of New Mexico. Serum and plasma samples for IL-1, IL-6, TNF-α and IL-10 and NTBI were obtained at baseline, 60 and 240 min after iron infusion. Peripheral blood mononuclear cells (PBMC) were isolated at the same time points and stained with fluorescent probes to identify intracellular reactive oxygen species and mitochondrial membrane potential (Δψm) by flow cytometry. Lipid peroxidation was assessed by plasma F(2) isoprostane concentration. Mean ± SEM maximum serum NTBI values were significantly higher among patients receiving IS compared to ID (2.59 ± 0.31 and 1.0 ± 0.36 µM, respectively, P = 0.005 IS vs. ID) Mean ± SEM NTBI area under the serum concentration-time curve (AUC) was 3-fold higher after IS versus ID (202 ± 53 vs. 74 ± 23 µM*min/l, P = 0.04) in ESRD patients, indicating increased exposure to NTBI. IV iron administration was associated with increased pro-inflammatory cytokines. Serum IL-6 concentrations increased most

  6. Mitochondrial alternative oxidase acts to dampen the generation of active oxygen species during a period of rapid respiration induced to support a high rate of nutrient uptake.

    PubMed

    Yip, Justine Y. H.; Vanlerberghe, Greg C.

    2001-07-01

    When wild type (wt) tobacco (Nicotiana tabacum L. cv. Petit Havana SR1) suspension cells were grown under phosphate (P) limitation, they contained large amounts of mitochondrial alternative oxidase (AOX). When these cells were resupplied with P, there was a large, immediate and sustained stimulation of respiration to support a period of rapid P uptake. Two lines of evidence suggest that the abundant level of AOX present in wt cells contributed to this stimulated rate of respiration. First, when P-limited transgenic antisense tobacco cells (AS8) lacking AOX were resupplied with P, the stimulation of respiration was much less dramatic even though these cells displayed similar rates of P uptake. Second, while the stimulated rate of respiration in AS8 cells was insensitive (as expected) to the AOX inhibitor n-propyl gallate (nPG), much of the stimulated rate of respiration in wt cells could be inhibited by nPG. Given the non-phosphorylating nature of AOX respiration, wt cells required higher rates of electron transport to O2 than AS8 cells to support similar rates of P uptake. The utilization of AOX by wt cells during P uptake was apparently not occurring because the cytochrome (Cyt) pathway alone could not fully support the rate of P uptake, as the respiration of cells lacking AOX (either untreated AS8 cells or wt cells treated with nPG) supported similar rates of P uptake as wt cells with abundant AOX. Rather, we provide in vivo evidence that the utilization of AOX during the period of high respiration supporting P uptake was to dampen the mitochondrial generation of active oxygen species (AOS).

  7. γ-tocotrienol prevents 5-FU-induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5-FU-induced activation of Nrf2

    PubMed Central

    TAKANO, HIDEYUKI; MOMOTA, YUKIHIRO; KANI, KOUICHI; AOTA, KEIKO; YAMAMURA, YOSHIKO; YAMANOI, TOMOKO; AZUMA, MASAYUKI

    2015-01-01

    Chemotherapy-induced oral mucositis is a common adverse event in patients with oral squamous cell carcinoma, and is initiated through a variety of mechanisms, including the generation of reactive oxygen species (ROS). In this study, we examined the preventive effect of γ-tocotrienol on the 5-FU-induced ROS production in human oral keratinocytes (RT7). We treated RT7 cells with 5-FU and γ-tocotrienol at concentrations of 10 μg/ml and 10 nM, respectively. When cells were treated with 5-FU alone, significant growth inhibition was observed as compared to untreated cells. This inhibition was, in part, due to the ROS generated by 5-FU treatment, because N-acetyl cysteine (NAC), a ROS scavenger, significantly ameliorated the growth of RT7 cells. γ-tocotrienol showed no cytotoxic effect on the growth of RT7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of ROS generation by γ-tocotrienol. Whereas 5-FU stimulated the expression of NF-E2-related factor 2 (Nrf2) protein in the nucleus up to 12 h after treatment of RT7 cells, γ-tocotrienol had no obvious effect on the expression of nuclear Nrf2 protein. Of note, the combined treatment with both agents stabilized the 5-FU-induced nuclear Nrf2 protein expression until 24 h after treatment. In addition, expression of Nrf2-dependent antioxidant genes, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO-1), was significantly augmented by treatment of cells with both agents. These findings suggest that γ-tocotrienol could prevent 5-FU-induced ROS generation by stabilizing Nrf2 activation, thereby leading to ROS detoxification and cell survival in human oral keratinocytes. PMID:25625649

  8. 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.

  9. 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.

  10. Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs

    PubMed Central

    2013-01-01

    Background Urban particulate matter (PM) has been epidemiologically correlated with multiple cardiopulmonary morbidities and mortalities, in sensitive populations. Children exposed to PM are more likely to develop respiratory infections and asthma. Although PM originates from natural and anthropogenic sources, vehicle exhaust rich in polycyclic aromatic hydrocarbons (PAH) can be a dominant contributor to the PM2.5 and PM0.1 fractions and has been implicated in the generation of reactive oxygen species (ROS). Objectives Current studies of ambient PM are confounded by the variable nature of PM, so we utilized a previously characterized ethylene-combusted premixed flame particles (PFP) with consistent and reproducible physiochemical properties and 1) measured the oxidative potential of PFP compared to ambient PM, 2) determined the ability of PFPs to generate oxidative stress and activate the transcription factor using in vitro and ex vivo models, and 3) we correlated these responses with antioxidant enzyme expression in vivo. Methods We compared oxidative stress response (HMOX1) and antioxidant enzyme (SOD1, SOD2, CAT, and PRDX6) expression in vivo by performing a time-course study in 7-day old neonatal and young adult rats exposed to a single 6-hour exposure to 22.4 μg/m3 PFPs. Results We showed that PFP is a potent ROS generator that induces oxidative stress and activates Nrf2. Induction of the oxidative stress responsive enzyme HMOX1 in vitro was mediated through Nrf2 activation and was variably upregulated in both ages. Furthermore, antioxidant enzyme expression had age and lung compartment variations post exposure. Of particular interest was SOD1, which had mRNA and protein upregulation in adult parenchyma, but lacked a similar response in neonates. Conclusions We conclude that PFPs are effective ROS generators, comparable to urban ambient PM2.5, that induce oxidative stress in neonatal and adult rat lungs. PFPs upregulate a select set of antioxidant enzymes in

  11. 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

  12. 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

  13. Activation of NOX2 by the stimulation of ionotropic and metabotropic glutamate receptors contributes to glutamate neurotoxicity in vivo through the production of reactive oxygen species and calpain activation.

    PubMed

    Guemez-Gamboa, Alicia; Estrada-Sánchez, Ana María; Montiel, Teresa; Páramo, Blanca; Massieu, Lourdes; Morán, Julio

    2011-11-01

    Prolonged activation of glutamate receptors leads to excitotoxicity. Several processes such as reactive oxygen species (ROS) production and activation of the calcium-dependent protease, calpain, contribute to glutamate-induced damage. It has been suggested that the ROS-producing enzyme, NADPH oxidase (NOX), plays a role in excitotoxicity. Studies have reported NOX activation after NMDA receptor stimulation during excitotoxic damage, but the role of non-NMDA and metabotropic receptors is unknown. We evaluated the roles of different glutamate receptor subtypes on NOX activation and neuronal death induced by the intrastriatal administration of glutamate in mice. In wild-type mice, NOX2 immunoreactivity in neurons and microglia was stimulated by glutamate administration, and it progressively increased as microglia became activated; calpain activity was also induced. By contrast, mice lacking NOX2 were less vulnerable to excitotoxicity, and there was reduced ROS production and protein nitrosylation, microglial reactivity, and calpain activation. These results suggest that NOX2 is stimulated by glutamate in neurons and reactive microglia through the activation of ionotropic and metabotropic receptors. Neuronal damage involves ROS production by NOX2, which, in turn, contributes to calpain activation.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Active oxygen doctors the evidence.

    PubMed

    Castelló, Ana; Francès, Francesc; Corella, Dolores; Verdú, Fernando

    2009-02-01

    Investigation at the scene of a crime begins with the search for clues. In the case of bloodstains, the most frequently used reagents are luminol and reduced phenolphthalein (or phenolphthalin that is also known as the Kastle-Meyer colour test). The limitations of these reagents have been studied and are well known. Household cleaning products have evolved with the times, and new products with active oxygen are currently widely used, as they are considered to be highly efficient at removing all kinds of stains on a wide range of surfaces. In this study, we investigated the possible effects of these new cleaning products on latent bloodstains that may be left at a scene of a crime. To do so, various fabrics were stained with blood and then washed using cleaning agents containing active oxygen. The results of reduced phenolphthalein, luminol and human haemoglobin tests on the washed fabrics were negative. The conclusion is that these new products alter blood to such an extent that it can no longer be detected by currently accepted methods employed in criminal investigations. This inability to locate bloodstains means that highly important evidence (e.g. a DNA profile) may be lost. Consequently, it is important that investigators are aware of this problem so as to compensate for it.

  20. 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.

  1. 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

  2. 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

  3. Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation.

    PubMed

    Kim, Ki Young; Ahn, Jin Hee; Cheon, Hyae Gyeong

    2007-09-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we elucidated the apoptotic mechanism of PPARgamma activation in human lung cancers by using a novel PPARgamma agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPARgamma activation selectively inhibited cell viability of non-small-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPARgamma activation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompanied by increased expression of proline oxidase (POX), a redox enzyme expressed in mitochondria, upon incubation with the agonists. POX RNA interference treatment blocked PPARgamma-induced ROS formation and cytotoxicity, suggesting that POX plays a functional role in apoptosis through ROS formation. The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl ether, a PPARgamma antagonist, and by knockdown of PPARgamma expression, indicating the involvement of PPARgamma in these actions. The results of the present study suggest that PPARgamma activation induces apoptotic cell death in non-small-cell lung carcinoma mainly through ROS formation via POX induction.

  4. 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.

  5. Reactive oxygen species-dependent HSP90 protein cleavage participates in arsenical As(+3)- and MMA(+3)-induced apoptosis through inhibition of telomerase activity via JNK activation.

    PubMed

    Shen, Shing-Chuan; Yang, Liang-Yo; Lin, Hui-Yi; Wu, Chin-Yen; Su, Tsung-Hsien; Chen, Yen-Chou

    2008-06-01

    The effects of six arsenic compounds including As(+3), MMA(+3), DMA(+3), As(+5), MMA(+5), and DMA(+5) on the viability of NIH3T3 cells were examined. As(+3) and MMA(+3), but not the others, exhibited significant cytotoxic effects in NIH3T3 cells through apoptosis induction. The apoptotic events such as DNA fragmentation and chromosome condensation induced by As(+3) and MMA(+3) were prevented by the addition of NAC and CAT, and induction of HO-1 gene expression in accordance with cleavage of the HSP90 protein, and suppression of telomerase activity were observed in NIH3T3 cells under As(+3) and MMA(+3) treatments. An increase in the intracellular peroxide level was examined in As(+3)- and MMA(+3)-treated NIH3T3 cells, and As(+3)- and MMA(+3)-induced apoptotic events were blocked by NAC, CAT, and DPI addition. HSP90 inhibitors, GA and RD, significantly attenuated the telomerase activity in NIH3T3 cells with an enhancement of As(+3)- and MMA(+3)-induced cytotoxicity. Suppression of JNKs significantly inhibited As(+3)- and MMA(+3)-induced apoptosis by blocking HSP90 protein cleavage and telomerase reduction in NIH3T3 cells. Furthermore, Hb, SnPP, and dexferosamine showed no effect against As(+3)- and MMA(+3)-induced apoptosis, and overexpression of HO-1 protein or inhibition of HO-1 protein expression did not affect the apoptosis induced by As(+3) or MMA(+3). These data provide the first evidence to indicate that apoptosis induced by As(+3) and MMA(+3) is mediated by an ROS-dependent degradation of HSP90 protein and reduction of telomerase via JNK activation, and HO-1 induction might not be involved.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Fisetin attenuates hydrogen peroxide-induced cell damage by scavenging reactive oxygen species and activating protective functions of cellular glutathione system.

    PubMed

    Kang, Kyoung Ah; Piao, Mei Jing; Kim, Ki Cheon; Cha, Ji Won; Zheng, Jian; Yao, Cheng Wen; Chae, Sungwook; Hyun, Jin Won

    2014-01-01

    Hydrogen peroxide (H2O2) can induce cell damage by generating reactive oxygen species (ROS), resulting in DNA damage and cell death. The aim of this study is to elucidate the protective effects of fisetin (3,7,3',4',-tetrahydroxy flavone) against H2O2-induced cell damage. Fisetin reduced the level of superoxide anion, hydroxyl radical in cell free system, and intracellular ROS generated by H2O2. Moreover, fisetin protected against H2O2-induced membrane lipid peroxidation, cellular DNA damage, and protein carbonylation, which are the primary cellular outcomes of H2O2 treatment. Furthermore, fisetin increased the level of reduced glutathione (GSH) and expression of glutamate-cysteine ligase catalytic subunit, which is decreased by H2O2. Conversely, a GSH inhibitor abolished the cytoprotective effect of fisetin against H2O2-induced cells damage. Taken together, our results suggest that fisetin protects against H2O2-induced cell damage by inhibiting ROS generation, thereby maintaining the protective role of the cellular GSH system.

  11. 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

  12. Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4

    PubMed Central

    Lee, Rosaline L.; Westendorf, Jens

    2007-01-01

    Background Antibodies produced by B-lymphocytes play a key role in the host defense against infection. The development, survival, and activation of B cell is regulated by multiple receptors including the B cell antigen receptor (BCR), which detects the presence of pathogens, CD40, which binds co-stimulatory molecules on activated T cells, and chemokines such as SDF-1 (CXCL12) that play key roles in B cell development and trafficking. Signaling by many receptors results in the generation of reactive oxygen species (ROS) that function as second messengers by regulating the activity of redox-sensitive kinases and phosphatases. We investigated the role of ROS in signaling by the BCR, CD40, and CXCR4, the receptor for SDF-1. We focused on activation of ERK, JNK, p38, and Akt, kinases that regulate multiple processes including cell survival, proliferation, and migration. Results Using the anti-oxidants N-acetyl L-cysteine (NAC) and ebselen to deplete intracellular ROS, we identified a differential requirement for ROS in the activation of ERK, JNK, p38, and Akt by these receptors. We found that CD40 activated JNK, p38, and Akt via redox-dependent pathways that were sensitive to ROS depletion by NAC and ebselen. In contrast, BCR-induced activation of ERK, JNK, p38, and Akt was not affected by ROS depletion. We also found that CXCR4-induced Akt activation was ROS-dependent even though activation of the ERK, JNK, and p38 MAP kinases by CXCR4 occurred via ROS-independent pathways. Conclusion The differential requirement for ROS in the activation of ERK, JNK, p38, and Akt by the BCR, CD40, and CXCR4 likely reflects the multiplicity of upstream activators for each of these kinases, only some of which may be regulated in a redox-dependent manner. These findings support the idea that ROS are important second messengers in B cells and suggest that oxidants or anti-oxidants could be used to modulate B cell activation. PMID:18481208

  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. 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.

  15. Apoptosis induction in human breast cancer (MCF-7) cells by a novel venom L-amino acid oxidase (Rusvinoxidase) is independent of its enzymatic activity and is accompanied by caspase-7 activation and reactive oxygen species production.

    PubMed

    Mukherjee, Ashis K; Saviola, Anthony J; Burns, Patrick D; Mackessy, Stephen P

    2015-10-01

    We report the elucidation of a mechanism of apoptosis induction in breast cancer (MCF-7) cells by an L-amino acid oxidase (LAAO), Rusvinoxidase, purified from the venom of Daboia russelii russelii. Peptide mass fingerprinting analysis of Rusvinoxidase, an acidic monomeric glycoprotein with a mass of ~57 kDa, confirmed its identity as snake venom LAAO. The enzymatic activity of Rusvinoxidase was completely abolished after two cycles of freezing and thawing; however, its cytotoxicity toward MCF-7 cells remained unaffected. Dose- and time-dependent induction of apoptosis by Rusvinoxidase on MCF-7 cells was evident from changes in cell morphology, cell membrane integrity, shrinkage of cells and apoptotic body formation accompanied by DNA fragmentation. Rusvinoxidase induced apoptosis in MCF-7 cells by both the extrinsic (death-receptor) and intrinsic (mitochondrial) signaling pathways. The former pathway of apoptosis operated through activation of caspase-8 that subsequently activated caspase-7 but not caspase-3. Rusvinoxidase-induced intrinsic pathway of apoptosis was accompanied by a time-dependent depolarization of the mitochondrial membrane through the generation of reactive oxygen species, followed by a decrease in cellular glutathione content and catalase activity, and down-regulation of expression of anti-apoptotic proteins Bcl-XL and heat-shock proteins (HSP-90 and HSP-70). Rusvinoxidase treatment resulted in increase of the pro-apoptotic protein Bax, subsequently leading to the release of cytochrome c from mitochondria to the cytosol and activating caspase-9, which in turn stimulated effector caspase-7. Rusvinoxidase at a dose of 4 mg/kg was non-toxic in mice, indicating that it may be useful as a model for the development of peptide-based anticancer drugs.

  16. Variation of antioxidative activity and growth enhancement of Brassicaceae induced by low-pressure oxygen plasma

    NASA Astrophysics Data System (ADS)

    Ono, Reoto; Hayashi, Nobuya

    2015-06-01

    The mechanism of growth enhancement induced by active oxygen species generated in an oxygen plasma is investigated. The plant growth enhancement induced by the active oxygen species would relate to an antioxidative activity, which is one of the biological responses. The amount of generated active oxygen species is varied by the oxygen gas pressure in a low-pressure RF glow discharge plasma. The antioxidative activity of sprouts of Brassicaceae induced by the oxygen plasma is maximized at pressures between 30 and 40 Pa, whereas the antioxidative activity becomes small at around 60 and 80 Pa. The pressure dependence of the antioxidative activity of sprout stems is opposite to that of the stem length of the sprouts. The growth enhancement would be induced by the increase in the concentration of active oxygen species in plants owing to the decrease in the amount of antioxidative substances.

  17. Isolation of Terpenoids from the Stem of Ficus aurantiaca Griff and their Effects on Reactive Oxygen Species Production and Chemotactic Activity of Neutrophils.

    PubMed

    Mawa, Shukranul; Jantan, Ibrahim; Husain, Khairana

    2016-01-05

    Three new triterpenoids; namely 28,28,30-trihydroxylupeol (1); 3,21,21,26-tetrahydroxy-lanostanoic acid (2) and dehydroxybetulinic acid (3) and seven known compounds; i.e., taraxerone (4); taraxerol (5); ethyl palmitate (6); herniarin (7); stigmasterol (8); ursolic acid (9) and acetyl ursolic acid (10) were isolated from the stem of Ficus aurantiaca Griff. The structures of the compounds were established by spectroscopic techniques. The compounds were evaluated for their inhibitory effects on polymorphonuclear leukocyte (PMN) chemotaxis by using the Boyden chamber technique and on human whole blood and neutrophil reactive oxygen species (ROS) production by using a luminol-based chemiluminescence assay. Among the compounds tested, compounds 1-4, 6 and 9 exhibited strong inhibition of PMN migration towards the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) with IC50 values of 6.8; 2.8; 2.5; 4.1; 3.7 and 3.6 μM, respectively, comparable to that of the positive control ibuprofen (6.7 μM). Compounds 2-4, 6, 7 and 9 exhibited strong inhibition of ROS production of PMNs with IC50 values of 0.9; 0.9; 1.3; 1.1; 0.5 and 0.8 μM, respectively, which were lower than that of aspirin (9.4 μM). The bioactive compounds might be potential lead molecules for the development of new immunomodulatory agents to modulate the innate immune response of phagocytes.

  18. Dopamine mediates striatal malonate toxicity via dopamine transporter-dependent generation of reactive oxygen species and D2 but not D1 receptor activation.

    PubMed

    Xia, X G; Schmidt, N; Teismann, P; Ferger, B; Schulz, J B

    2001-10-01

    Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate results in both chemically induced hypoxia and striatal lesions that are similar to those seen in Huntington's disease and cerebral ischaemia. The mechanisms leading to neuronal death involve secondary excitotoxicity, the release of dopamine from nigrostriatal fibres and the generation of reactive oxygen species (ROS) including nitric oxide (NO) and hydroxyl radicals. Here, we further investigated the contribution and mechanism of dopamine on malonate-induced striatal lesions. Prior lesions of the nigrostriatal pathway with 6-OHDA or the depletion of striatal dopamine stores by pretreatment with reserpine, an inhibitor or the vesicular monoamine transporter type-2 (VMAT2), in combination with alpha-methyl-p-tyrosine resulted in a significant reduction of malonate-induced striatal lesion volumes. This was paralleled by block or reduction of the malonate-induced generation of ROS, as measured by the conversions of salicylate to 2,3-dihydroxybenzoic acid (2,3-DHBA) using microdialysis. Systemic or intrastriatal application of L-DOPA or dopamine, respectively, reconstituted malonate toxicity and the generation of ROS in 6-OHDA-lesioned rats. Block of the dopamine transporter by GBR12909 did not result in a reduction of malonate-induced dopamine release, but significantly reduced the generation of hydroxyl radicals. The D2 receptor agonist lisuride and the mixed D1 and D2 receptor agonist apomorphine, but not the D1 receptor agonist SKF38393, partially restored malonate toxicity in 6-OHDA-lesioned rats without increasing the generation of ROS. In line with these results sulpiride, an inhibitor of D2 receptors, reduced the malonate-induced lesion volume, whereas SCH23390, an inhbitor of D1 receptors, was ineffective. Our data suggest that malonate-induced dopamine toxicity to energetically impaired neurons is mediated by two independent pathways: (i) dopamine transporter uptake

  19. 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.

  20. 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.

  1. Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance.

    PubMed

    Chakraborty, Jayashree B; Mahato, Sanjit K; Joshi, Kalpana; Shinde, Vaibhav; Rakshit, Srabanti; Biswas, Nabendu; Choudhury Mukherjee, Indrani; Mandal, Labanya; Ganguly, Dipyaman; Chowdhury, Avik A; Chaudhuri, Jaydeep; Paul, Kausik; Pal, Bikas C; Vinayagam, Jayaraman; Pal, Churala; Manna, Anirban; Jaisankar, Parasuraman; Chaudhuri, Utpal; Konar, Aditya; Roy, Siddhartha; Bandyopadhyay, Santu

    2012-01-01

    Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings.

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

    NASA Astrophysics Data System (ADS)

    Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

    2014-09-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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...

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

    PubMed Central

    Catalani, Simona; Galati, Rossella

    2015-01-01

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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  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. 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

  2. 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.

  3. Oxygen in activator centers of zinc sulfide

    SciTech Connect

    Golobeva, N.P.; Fok, M.V.

    1986-05-01

    The authors observed the sensitized luminescence of Tm and Dy without addition of Cu and Ag in samples which had been obtained by the sulfonation of zinc sulfide in hydrogen sulfide; the zinc sulfide has a copper concentration below 5.10/sup -6/ mass %. In this case the excitation can be transmitted from the ZnS lattice to the rare-earth activators mainly through defects including oxygen. The following conclusions were made. In the case of activated ZnS, oxygen is present in formations accounting for the excitation and luminescence of a number of luminophors. When an activator is introduced in the region of ZnS layer faults, where also the oxygen must be located, the positioning of the faults in close vicinity is facilitated even when the oxygen concentration of the ZnS is low. All this must be considered when models of luminescence centers of zinc sulfide are developed.

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

    PubMed

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

    2016-01-01

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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Silibinin activates AMP-activated protein kinase to protect neuronal cells from oxygen and glucose deprivation-re-oxygenation.

    PubMed

    Xie, Zhi; Ding, Sheng-quan; Shen, Ya-fang

    2014-11-14

    In this study, we explored the cytoprotective potential of silibinin against oxygen-glucose deprivation (OGD)-induced neuronal cell damages, and studied underling mechanisms. In vitro model of ischemic stroke was created by keeping neuronal cells (SH-SY5Y cells and primary mouse cortical neurons) in an OGD condition followed by re-oxygenation. Pre-treatment of silibinin significantly inhibited OGD/re-oxygenation-induced necrosis and apoptosis of neuronal cells. OGD/re-oxygenation-induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) reduction were also inhibited by silibinin. At the molecular level, silibinin treatment in SH-SY5Y cells and primary cortical neurons led to significant AMP-activated protein kinase (AMPK) signaling activation, detected by phosphorylations of AMPKα1, its upstream kinase liver kinase B1 (LKB1) and the downstream target acetyl-CoA Carboxylase (ACC). Pharmacological inhibition or genetic depletion of AMPK alleviated the neuroprotective ability of silibinin against OGD/re-oxygenation. Further, ROS scavenging ability by silibinin was abolished with AMPK inhibition or silencing. While A-769662, the AMPK activator, mimicked silibinin actions and suppressed ROS production and neuronal cell death following OGD/re-oxygenation. Together, these results show that silibinin-mediated neuroprotection requires activation of AMPK signaling.

  13. 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...

  14. 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...

  15. 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

  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. 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.

  18. Pinellia ternata lectin exerts a pro-inflammatory effect on macrophages by inducing the release of pro-inflammatory cytokines, the activation of the nuclear factor-κB signaling pathway and the overproduction of reactive oxygen species.

    PubMed

    Yu, Hong-Li; Zhao, Teng-Fei; Wu, Hao; Pan, Yao-Zong; Zhang, Qian; Wang, Kui-Long; Zhang, Chen-Chao; Jin, Yang-Ping

    2015-10-01

    Pinellia ternata (PT) is a widely used traditional Chinese medicine. The raw material has a throat-irritating toxicity that is associated with the PT lectin (PTL). PTL is a monocot lectin isolated from the tubers of PT, which exhibits mouse peritoneal acute inflammatory effects in vivo. The present study aimed to investigate the pro-inflammatory effect of PTL on macrophages. PTL (50 µg/ml)‑stimulated macrophages enhanced the chemotactic activity of neutrophils. PTL (50, 100, 200 and 400 µg/ml) significantly elevated the production of cytokines [tumor necrosis factor‑α (TNF-α) , interleukin (IL)‑1β and IL‑6]. PTL (25, 50 and 100 µg/ml) induced intracellular reactive oxygen species (ROS) overproduction. PTL also caused transfer of p65 from the macrophage cytoplasm to the nucleus and activated the nuclear factor‑κB (NF‑κB) signaling pathway. Scanning electron microscope images revealed severe cell swelling and membrane integrity defection of macrophages following PTL (100 µg/ml) stimulation, which was also associated with inflammation. PTL had pro‑inflammatory activity, involving induced neutrophil migration, cytokine release, ROS overproduction and the activation of the NF-κB signaling pathway, which was associated with the activation of macrophages.

  19. 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

  20. Changes in the antioxidant systems as part of the signaling pathway responsible for the programmed cell death activated by nitric oxide and reactive oxygen species in tobacco Bright-Yellow 2 cells.

    PubMed

    de Pinto, Maria Concetta; Tommasi, Franca; De Gara, Laura

    2002-10-01

    Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS), for the activation of the hypersensitive reaction, a defense response induced in the noncompatible plant-pathogen interaction. However, its involvement in activating programmed cell death (PCD) in plant cells has been questioned. In this paper, the involvement of the cellular antioxidant metabolism in the signal transduction triggered by these bioactive molecules has been investigated. NO and ROS levels were singularly or simultaneously increased in tobacco (Nicotiana tabacum cv Bright-Yellow 2) cells by the addition to the culture medium of NO and/or ROS generators. The individual increase in NO or ROS had different effects on the studied parameters than the simultaneous increase in the two reactive species. NO generation did not cause an increase in phenylalanine ammonia-lyase (PAL) activity or induction of cellular death. It only induced minor changes in ascorbate (ASC) and glutathione (GSH) metabolisms. An increase in ROS induced oxidative stress in the cells, causing an oxidation of the ASC and GSH redox pairs; however, it had no effect on PAL activity and did not induce cell death when it was generated at low concentrations. In contrast, the simultaneous increase of NO and ROS activated a process of death with the typical cytological and biochemical features of hypersensitive PCD and a remarkable rise in PAL activity. Under the simultaneous generation of NO and ROS, the cellular antioxidant capabilities were also suppressed. The involvement of ASC and GSH as part of the transduction pathway leading to PCD is discussed.

  1. Regulator of G Protein Signaling 6 (RGS6) Mediates Doxorubicin-induced ATM and p53 Activation by a Reactive Oxygen Species (ROS)-dependent Mechanism

    PubMed Central

    Huang, Jie; Yang, Jianqi; Maity, Biswanath; Mayuzumi, Daisuke; Fisher, Rory A.

    2011-01-01

    Doxorubicin (DXR), among the most widely used cancer chemotherapy agents, promotes cancer cell death via activation of ATM and the resultant up-regulation of tumor suppressor p53. The exact mechanism by which DXR activates ATM is not fully understood. Here we discovered a novel role for Regulator of G protein Signaling 6 (RGS6) in mediating activation of ATM and p53 by DXR. RGS6 was robustly induced by DXR, and genetic loss of RGS6 dramatically impaired DXR-induced activation of ATM and p53, as well as its in vivo apoptotic actions in heart. The ability of RGS6 to promote p53 activation in response to DXR was independent of RGS6 interaction with G proteins but required ATM. RGS6 mediated activation of ATM and p53 by DXR via a ROS-dependent and DNA damage-independent mechanism. This mechanism represents the primary means by which DXR promotes activation of the ATM-p53-apoptosis pathway that underlies its cytotoxic activity. Our findings contradict the canonical theories that DXR activates ATM primarily by promoting DNA damage either directly or indirectly (via ROS) and that RGS6 function is mediated by its interactions with G proteins. These findings reveal a new mechanism for the chemotherapeutic actions of DXR and identify RGS6 as a novel target for cancer chemotherapy. PMID:21859827

  2. Mdivi-1 prevents apoptosis induced by ischemia-reperfusion injury in primary hippocampal cells via inhibition of reactive oxygen species-activated mitochondrial pathway.

    PubMed

    Wang, Jinying; Wang, Peng; Li, Shuhong; Wang, Shilei; Li, Yu; Liang, Nan; Wang, Min

    2014-07-01

    Apoptosis is one of the major mechanisms of neuronal injury during ischemic-reperfusion (I/R). Mitochondrial division inhibitor (mdivi-1) is a selective inhibitor of mitochondrial fission protein Drp1. The previous experiments support that mdivi-1 reduce I/R injury in the heart model of rat, but the neuroprotective effect of the mdivi-1 is not yet clearly defined at the cellular levels in brain. In our present study, we estimated a brain model of I/R injury in vitro by subjecting oxygen and glucose deprivation (OGD) followed by reoxygenation to the cultured rat primary hippocampal cells, which aimed to find the neuroprotective mechanism of mdivi-1. The cell was pretreated with mdivi-1 for 40 minutes and then ischemia for 6 hours followed by reperfusion for 20 hours. The redox state, cell apoptosis, and expression of Drp1, Bcl-2, Bax, and cytochrome C proteins were measured. The data showed that administration of mdivi-1 at the doses of 50 μM significantly reduced oxidative stress, attenuated cell apoptosis, upregulated Bcl-2 expression, and downregulated Drp1, Bax, and cytochrome C expression. The results suggested that mdivi-1 protected brain from OGD reperfusion injury, which through suppressing the ROS initiated mitochondrial pathway.

  3. Single-cell analysis of dihydroartemisinin-induced apoptosis through reactive oxygen species-mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques

    NASA Astrophysics Data System (ADS)

    Lu, Ying-Ying; Chen, Tong-Sheng; Wang, Xiao-Ping; Li, Li

    2010-07-01

    Dihydroartemisinin (DHA), a front-line antimalarial herbal compound, has been shown to possess promising anticancer activity with low toxicity. We have previously reported that DHA induced caspase-3-dependent apoptosis in human lung adenocarcinoma cells. However, the cellular target and molecular mechanism of DHA-induced apoptosis is still poorly defined. We use confocal fluorescence microscopy imaging, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching techniques to explore the roles of DHA-elicited reactive oxygen species (ROS) in the DHA-induced Bcl-2 family proteins activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS-mediated apoptosis. Confocal imaging analysis in a single living cell and Western blot assay showed that DHA triggered ROS-dependent Bax translocation, mitochondrial membrane depolarization, alteration of mitochondrial morphology, cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating the coexistence of ROS-mediated mitochondrial and death receptor pathway. Collectively, our findings demonstrate for the first time that DHA induces cell apoptosis by triggering ROS-mediated caspase-8/Bid activation and the mitochondrial pathway, which provides some novel insights into the application of DHA as a potential anticancer drug and a new therapeutic strategy by targeting ROS signaling in lung adenocarcinoma therapy in the future.

  4. HISTONE DEACETYLASE ACTIVITY AND REACTIVE OXYGEN SPECIES CONTENT IN THE TISSUE CULTURE OF Arabidopsis thaliana UNDER NORMAL CONDITIONS AND DEVELOPMENT OF ACUTE OSMOTIC STRESS.

    PubMed

    Jadko, S I

    2015-01-01

    The possible involvement of histone deacetylase (HDAC) in regulation of ROS content in the tissue culture of Arabidopsis thaliana under normal conditions and under development of acute osmotic stress was studied by using inhibition assay with application of trichostatin A (TSA). It was found that in the tissue culture grown under normal conditions a decrease in HDAC activity by means of TSA led to increase of the ROS content. Similar but more pronounced alterations occurred under stress. At the same time an increase in histone acetyltransferase (HAT) activity was also observed. The possible mechanisms of HDAC and HAT participation in regulation of ROS content by changes in expression of genes that are responsible for ROS production and antioxidant activity are discussed.

  5. 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

  6. Inflammasome activation is reactive oxygen species dependent and mediates irinotecan-induced mucositis through IL-1β and IL-18 in mice.

    PubMed

    Arifa, Raquel D N; Madeira, Mila F M; de Paula, Talles P; Lima, Renata L; Tavares, Livia D; Menezes-Garcia, Zélia; Fagundes, Caio T; Rachid, Milene A; Ryffel, Bernhard; Zamboni, Dario S; Teixeira, Mauro M; Souza, Danielle G

    2014-07-01

    Irinotecan is a useful chemotherapeutic for the treatment of various cancers. Irinotecan treatment is associated with mucositis, which clearly limits the use of the drug. Mechanisms that account for mucositis are only partially known. This study assessed mechanisms and the role of inflammasome activation in irinotecan-induced mucositis. Mucositis in mice was induced by irinotecan injection in C57BL/6 wild-type, gp91phox(-/-), il-18(-/-), casp-1(-/-), and asc(-/-) mice once a day for 4 consecutive days. In some experiments, mice received apocynin to inhibit NADPH oxidase (NOX), IL-1 receptor antagonist, or IL-18 binding protein to prevent activation of IL-1 and IL-18 receptors, respectively. Mice were euthanized 7 days after the beginning of irinotecan treatment, and small intestines were collected for analysis. Irinotecan treatment resulted in increased IL-1β and IL-18 production in ileum and NOX-2-dependent oxidative stress. gp91phox(-/-) and apocynin-treated mice had diminished oxidative stress and less severe mucositis. Furthermore, treatment with apocynin decreased caspase-1 activation and IL-1β and IL-18 production in the ileum. asc(-/-) and casp-1(-/-) mice also had less intestinal injury and decreased IL-1β and IL-18 production. Finally, both the absence of IL-18 and IL-1β resulted in reduced inflammatory response and attenuated intestinal injury. NOX-2-derived oxidative stress mediates inflammasome activation and inflammasome-dependent production of IL-1β and IL-18, which mediate tissue injury during irinotecan-induced mucositis in mice.

  7. Effects of taxifolin on the activity of angiotensin-converting enzyme and reactive oxygen and nitrogen species in the aorta of aging rats and rats treated with the nitric oxide synthase inhibitor and dexamethasone.

    PubMed

    Arutyunyan, Tamara V; Korystova, Antonina F; Kublik, Ludmila N; Levitman, Maria Kh; Shaposhnikova, Vera V; Korystov, Yuri N

    2013-12-01

    The action of taxifolin on the angiotensin-converting enzyme (ACE) and the formation of reactive oxygen and nitrogen species (ROS/RNS) in the aorta of aging rats and rats treated with nitric oxide synthase inhibitor (N ω-nitro-L-arginine methyl ester (L-NAME)) or dexamethasone have been studied. The ACE activity in aorta sections was determined by measuring the hydrolysis of hippuryl-L-histidyl-L-leucine, and the ROS/RNS production was measured by oxidation of dichlorodihydrofluorescein. It was shown that taxifolin at a dose of 30-100 μg/kg/day decreases the ACE activity in the aorta of aging rats and of rats treated with L-NAME or dexamethasone to the level of the ACE activity in young control rats. Taxifolin (100 μg/kg/day) was found to also reduce the amount of ROS/RNS in the aorta that increased as a result of L-NAME intake. L-NAME treatment increases the contribution of 5-lipoxygenase and NADPH oxidase to ROS/RNS production in the aorta, while taxifolin (100 μg/kg/day) decreases the contribution of these enzymes to the normal level.

  8. Renin-angiotensin system acting on reactive oxygen species in paraventricular nucleus induces sympathetic activation via AT1R/PKCγ/Rac1 pathway in salt-induced hypertension

    PubMed Central

    Su, Qing; Huo, Chan-Juan; Li, Hong-Bao; Liu, Kai-Li; Li, Xiang; Yang, Qing; Song, Xin-Ai; Chen, Wen-Sheng; Cui, Wei; Zhu, Guo-Qing; Shi, Xiao-Lian; Liu, Jin-Jun; Kang, Yu-Ming

    2017-01-01

    Brain renin-angiotensin system (RAS) could regulate oxidative stress in the paraventricular nucleus (PVN) in the development of hypertension. This study was designed to explore the precise mechanisms of RAS acting on reactive oxygen species (ROS) in salt-induced hypertension. Male Wistar rats were administered with a high-salt diet (HS, 8.0% NaCl) for 8 weeks to induced hypertension. Those rats were received PVN infusion of AT1R antagonist losartan (LOS, 10 μg/h) or microinjection of small interfering RNAs for protein kinase C γ (PKCγ siRNA) once a day for 2 weeks. High salt intake resulted in higher levels of AT1R, PKCγ, Rac1 activity, superoxide and malondialdehyde (MDA) activity, but lower levels of copper/zinc superoxide dismutase (Cu/Zn-SOD), superoxide dismutase (SOD) and glutathione (GSH) in PVN than control animals. PVN infusion of LOS not only attenuated the PVN levels of AT1R, PKCγ, Rac1 activity, superoxide and decreased the arterial pressure, but also increased the PVN antioxidant capacity in hypertension. PVN microinjection of PKCγ siRNA had the same effect on LOS above responses to hypertension but no effect on PVN level of AT1R. These results, for the first time, identified that the precise signaling pathway of RAS regulating ROS in PVN is via AT1R/PKCγ/Rac1 in salt-induced hypertension. PMID:28338001

  9. Deuterohemin-AlaHisLys mitigates the symptoms of rats with non-insulin dependent diabetes mellitus by scavenging reactive oxygen species and activating the PI3-K/AKT signal transduction pathway.

    PubMed

    Lei, Liyan; Zhang, Guangji; Li, Pengfei; Zhang, Yuan; Guo, Youming; Zhang, Wenqi; Zhang, Wenbo; Hu, Bing; Wang, Liping

    2014-09-05

    Damage to pancreatic β-cells plays an important role in the development of type 2 diabetes, and oxidative stress is a likely contributor. In the present study, we investigated the effect of deuterohemin-AlaHisLys (DhHP-3), a microperoxidase-11 mimic, on rats with non-insulin dependent diabetes mellitus and examined the action mechanisms of DhHP-3. The induced hyperglycemia, glucose intolerance, and insulin resistance in diabetic rats were associated with increased oxidative stress and damage to pancreatic islets. DhHP-3 (3 mg/kg) ameliorated hyperglycemia and insulin resistance, protected pancreas islet, decreased the content of malondialdehyde, and increased the activity of superoxide dismutase in plasma and pancreatic tissue by reducing ROS levels. Furthermore, DhHP-3 stimulated the proliferation of INS-1 cells and inhibited apoptosis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3-K/AKT) signaling pathway. Our results demonstrated for the first time that DhHP-3 decreased blood glucose level in rats with non-insulin dependent diabetes mellitus, scavenged reactive oxygen species, activated the PI3-K/AKT signaling pathway, and protected pancreatic β-cells against apoptosis.

  10. Study on the interaction of ions of transient metals with ascorbic acid in the presence of different scavengers of active oxygen species in SOS chromotest.

    PubMed

    Marczewska, Jadwiga; Koziorowska, Jadwiga H

    2002-03-01

    SOS chromotest was employed to study the interaction of ascorbic acid with free ions of transient metals in the presence of added catalase, superoxide dismutase or D-mannitol. Catalase diminished the genotoxic activity of the mixture of ascorbic acid with copper ions in E. coli strains PQ37 and PQ 300, but genotoxicity of this mixture was not suppressed by superoxide dismutase and D-mannitol. The results suggest that copper ions diminished the content of peroxide generated by ascorbic acid.

  11. Isorhamnetin inhibits H₂O₂-induced activation of the intrinsic apoptotic pathway in H9c2 cardiomyocytes through scavenging reactive oxygen species and ERK inactivation.

    PubMed

    Sun, Bing; Sun, Gui-Bo; Xiao, Jing; Chen, Rong-Chang; Wang, Xin; Wu, Ying; Cao, Li; Yang, Zhi-Hong; Sun, Xiao-Bo

    2012-02-01

    As a traditional Chinese medicine, the sea buckthorn (Hippophae rhamnoides L.) has a long history in the treatment of ischemic heart disease and circulatory disorders. However, the active compounds responsible for and the underlying mechanisms of these effects are not fully understood. In this article, isorhamnetin pretreatment counteracted H(2)O(2)-induced apoptotic damage in H9c2 cardiomyocytes. Isorhamnetin did not inhibit the death receptor-dependent or extrinsic apoptotic pathways, as characterized by its absence in both caspase-8 inactivation and tBid downregulation along with unchanged Fas and TNFR1 mRNA levels. Instead, isorhamnetin specifically suppressed the mitochondria-dependent or intrinsic apoptotic pathways, as characterized by inactivation of caspase-9 and -3, maintenance of the mitochondrial membrane potential (ΔΨm), and regulation of a series of Bcl-2 family genes upstream of ΔΨm. The anti-apoptotic effects of isorhamnetin were linked to decreased ROS generation. H(2)O(2) activated ERK and p53, whereas isorhamnetin inhibited their activation. ERK overexpression overrode the isorhamnetin-induced inhibition of the intrinsic apoptotic pathway in H9c2 cardiomyocytes, which indicated that an ERK-dependent pathway was involved. Furthermore, N-acetyl cysteine (a potent ROS scavenger) could attenuate the H(2)O(2)-induced apoptosis. However, PD98059 (an ERK-specific inhibitor) could not effectively antagonize ROS generation, which indicates that ROS may be an upstream inducer of ERK. In conclusion, isorhamnetin inhibits the H(2)O(2)-induced activation of the intrinsic apoptotic pathway via ROS scavenging and ERK inactivation. Therefore, isorhamnetin is a promising reagent for the treatment of ROS-induced cardiomyopathy.

  12. Peroxisome Proliferator-Activated Receptor (PPAR) γ and PPARα Agonists Modulate Mitochondrial Fusion-Fission Dynamics: Relevance to Reactive Oxygen Species (ROS)-Related Neurodegenerative Disorders?

    PubMed Central

    Zolezzi, Juan M.; Silva-Alvarez, Carmen; Ordenes, Daniela; Godoy, Juan A.; Carvajal, Francisco J.; Santos, Manuel J.; Inestrosa, Nibaldo C.

    2013-01-01

    Recent studies showed that the activation of the retinoid X receptor, which dimerizes with peroxisome proliferator-activated receptors (PPARs), leads to an enhanced clearance of Aβ from the brain of transgenic mice model of Alzheimer’s disease (AD), because an increased expression of apolipoprotein E and it main transporters. However, the effects observed must involve additional underlying mechanisms that have not been yet explored. Several studies conducted in our laboratory suggest that part of the effects observed for the PPARs agonist might involves mitochondrial function and, particularly, mitochondrial dynamics. In the present study we assessed the effects of oxidative stress challenge on mitochondrial morphology and mitochondrial dynamics-related proteins in hippocampal neurons. Using immunofluorescence, we evaluated the PPARγ co-activator 1α (PGC-1α), dynamin related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), and mitochondrial length, in order to determine if PPARs agonist pre-treatment is able to protect mitochondrial population from hippocampal neurons through modulation of the mitochondrial fusion-fission events. Our results suggest that both a PPARγ agonist (ciglitazone) and a PPARα agonist (WY 14.643) are able to protect neurons by modulating mitochondrial fusion and fission, leading to a better response of neurons to oxidative stress, suggesting that a PPAR based therapy could acts simultaneously in different cellular components. Additionally, our results suggest that PGC-1α and mitochondrial dynamics should be further studied in future therapy research oriented to ameliorate neurodegenerative disorders, such as AD. PMID:23675519

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  14. Functional characterization of NAC55 transcription factor from oilseed rape (Brassica napus L.) as a novel transcriptional activator modulating reactive oxygen species accumulation and cell death.

    PubMed

    Niu, Fangfang; Wang, Chen; Yan, Jingli; Guo, Xiaohua; Wu, Feifei; Yang, Bo; Deyholos, Michael K; Jiang, Yuan-Qing

    2016-09-01

    NAC transcription factors (TFs) are plant-specific and play important roles in development, responses to biotic and abiotic cues and hormone signaling. So far, only a few NAC genes have been reported to regulate cell death. In this study, we identified and characterized a NAC55 gene isolated from oilseed rape (Brassica napus L.). BnaNAC55 responds to multiple stresses, including cold, heat, abscisic acid (ABA), jasmonic acid (JA) and a necrotrophic fungal pathogen Sclerotinia sclerotiorum. BnaNAC55 has transactivation activity and is located in the nucleus. BnaNAC55 is able to form homodimers in planta. Unlike ANAC055, full-length BnaNAC55, but not either the N-terminal NAC domain or C-terminal regulatory domain, induces ROS accumulation and hypersensitive response (HR)-like cell death when expressed both in oilseed rape protoplasts and Nicotiana benthamiana. Furthermore, BnaNAC55 expression causes obvious nuclear DNA fragmentation. Moreover, quantitative reverse transcription PCR (qRT-PCR) analysis identified that the expression levels of multiple genes regulating ROS production and scavenging, defense response as well as senescence are significantly induced. Using a dual luciferase reporter assay, we further confirm that BnaNAC55 could activate the expression of a few ROS and defense-related gene expression. Taken together, our work has identified a novel NAC TF from oilseed rape that modulates ROS accumulation and cell death.

  15. Data in the activities of caspases and the levels of reactive oxygen species and cytochrome c in the •OH-induced fish erythrocytes treated with alanine, citrulline, proline and their combination

    PubMed Central

    Li, Huatao; Jiang, Weidan; Liu, Yang; Jiang, Jun; Zhang, Yongan; Wu, Pei; Zhao, Juan; Duan, Xudong; Zhou, Xiaoqiu; Feng, Lin

    2016-01-01

    The present study explored the effects of alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala10Pro4Cit1) on the activities of caspases and levels of reactive oxygen species (ROS) and cytochrome c in hydroxyl radicals (•OH)-induced carp erythrocytes. The data displayed that •OH induced the increases in the activities of caspase−3, caspase−8 and caspase−9 and the levels of ROS and cytochrome c in carp erythrocytes. However, Ala, Cit, Pro and Ala10Pro4Cit1 effectively suppressed the •OH-induced increases in the activities of caspase−3, caspase−8 and caspase−9 and the levels of ROS and cytochrome c in carp erythrocytes. Furthermore, the activities of caspase−3, caspase−8 and caspase−9 and the levels of ROS and cytochrome c were gradually decreased with increasing concentrations of Ala, Cit, Pro and Ala10Pro4Cit1 (0.175−1.400 mM) in the •OH-induced carp erythrocytes. These data demonstrated that the 50% inhibitory doses (ID50) of Ala10Pro4Cit1 on the activities of caspase−8, caspase−9 and caspase−3 and levels of ROS and cytochrome c were respectively estimated to be the minimum values among amino acids examined so far. The 5% inhibitory doses (ID5) of Ala, Cit, Pro and Ala10Pro4Cit1 on the activities of caspase−8, caspase−9 and caspase−3 and levels of ROS and cytochrome c were estimated to be at their physiological concentrations in mammalian. Our research article for further interpretation and discussion from these data in Li et al. (2016) [1]. PMID:26952131

  16. Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production, activating NF-κB signaling, and promoting fibroblast-to-myofibroblast transformation.

    PubMed

    He, Xiaoqing; Young, Shih-Houng; Schwegler-Berry, Diane; Chisholm, William P; Fernback, Joseph E; Ma, Qiang

    2011-12-19

    Carbon nanotubes (CNTs) are novel materials with unique electronic and mechanical properties. The extremely small size, fiberlike shape, large surface area, and unique surface chemistry render their distinctive chemical and physical characteristics and raise potential hazards to humans. Several reports have shown that pulmonary exposure to CNTs caused inflammation and lung fibrosis in rodents. The molecular mechanisms that govern CNT lung toxicity remain largely unaddressed. Here, we report that multiwalled carbon nanotubes (MWCNTs) have potent, dose-dependent toxicity on cultured human lung cells (BEAS-2B, A549, and WI38-VA13). Mechanistic analyses were carried out at subtoxic doses (≤20 μg/mL, ≤ 24 h). MWCNTs induced substantial ROS production and mitochondrial damage, implicating oxidative stress in cellular damage by MWCNT. MWCNTs activated the NF-κB signaling pathway in macrophages (RAW264.7) to increase the secretion of a panel of cytokines and chemokines (TNFα, IL-1β, IL-6, IL-10, and MCP1) that promote inflammation. Activation of NF-κB involved rapid degradation of IκBα, nuclear accumulation of NF-κBp65, binding of NF-κB to specific DNA-binding sequences, and transactivation of target gene promoters. Finally, MWCNTs induced the production of profibrogenic growth factors TGFβ1 and PDGF from macrophages that function as paracrine signals to promote the transformation of lung fibroblasts (WI38-VA13) into myofibroblasts, a key step in the development of fibrosis. Our results revealed that MWCNTs elicit multiple and intertwining signaling events involving oxidative damage, inflammatory cytokine production, and myofibroblast transformation, which potentially underlie the toxicity and fibrosis in human lungs by MWCNTs.

  17. 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

  18. 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.

  19. Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2.

    PubMed

    Ma, Qiang; Battelli, Lori; Hubbs, Ann F

    2006-06-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant-activated cap "n" collar basic leucine zipper transcription factor. To assess the function of Nrf2 in the antioxidant response, we examined mice with targeted disruption of the Nrf2 gene. Nrf2-null mice developed complex disease manifestations, with a majority exhibiting a lupus-like autoimmune syndrome characterized by multiorgan inflammatory lesions with a marked female predominance, appearance of anti-double-stranded DNA antibodies in young adulthood, intravascular deposition of immunoglobulin complexes in blood vessels, and premature death due to rapidly progressing membranoproliferative glomerular nephritis. Mechanistic analyses revealed that the null mice showed enhanced proliferative response of CD4+ T cells, altered ratios of CD4+ and CD8+ cells, and increased oxidative lesions in tissues. Analyses of antioxidant-induced gene expression showed that the knockout mice were devoid of the basal and inducible expression of certain phase 2 detoxification enzymes and antioxidant genes in hepatic and lymphoid cells in vivo. Our findings suggest that Nrf2 mediates important antioxidant functions involved in the control of peripheral lymphocyte homeostasis and autoimmune surveillance.

  20. Simvastatin rises reactive oxygen species levels and induces senescence in human melanoma cells by activation of p53/p21 pathway

    SciTech Connect

    Guterres, Fernanda Augusta de Lima Barbosa; Martinez, Glaucia Regina; Rocha, Maria Eliane Merlin; Winnischofer, Sheila Maria Brochado

    2013-11-15

    Recent studies demonstrated that simvastatin has antitumor properties in several types of cancer cells, mainly by inducing apoptosis and inhibiting growth. The arrest of proliferation is a feature of cellular senescence; however, the occurrence of senescence in melanoma cells upon simvastatin treatment has not been investigated until now. Our results demonstrated that exposure of human metastatic melanoma cells (WM9) to simvastatin induces a senescent phenotype, characterized by G1 arrest, positive staining for senescence-associated β-galactosidase assay, and morphological changes. Also, the main pathways leading to cell senescence were examined in simvastatin-treated human melanoma cells, and the expression levels of phospho-p53 and p21 were upregulated by simvastatin, suggesting that cell cycle regulators and DNA damage pathways are involved in the onset of senescence. Since simvastatin can act as a pro-oxidant agent, and oxidative stress may be related to senescence, we measured the intracellular ROS levels in WM9 cells upon simvastatin treatment. Interestingly, we found an increased amount of intracellular ROS in these cells, which was accompanied by elevated expression of catalase and peroxiredoxin-1. Collectively, our results demonstrated that simvastatin can induce senescence in human melanoma cells by activation of p53/p21 pathway, and that oxidative stress may be related to this process. - Highlights: • Lower concentrations of simvastatin can induce senescent phenotype in melanoma cells. • Simvastatin induces senescence in human melanoma cells via p53/p21 pathway. • Senescent phenotype is related with increased intracellular ROS. • Partial detoxification of ROS by catalase/peroxiredoxin-1 could lead cells to senescence rather than apoptosis.

  1. Inhibitory effect of butein on tumor necrosis factor-α-induced expression of cell adhesion molecules in human lung epithelial cells via inhibition of reactive oxygen species generation, NF-κB activation and Akt phosphorylation.

    PubMed

    Jang, Ji Hoon; Yang, Eun Sun; Min, Kyoung-Jin; Kwon, Taeg Kyu

    2012-12-01

    Cell adhesion molecules play an important role in inflammatory response, angiogenesis and tumor progression. Butein (tetrahydroxychalcone) is a small molecule from natural sources, known to be a potential therapeutic drug with anti-inflammatory, anticancer and antioxidant activities. In the present study, we investigated the inhibitory effect of butein on tumor necrosis factor (TNF)-α-induced adhesion molecule expression and its molecular mechanism of action. Butein significantly decreased TNF-α-induced monocyte (U937) cell adhesion to lung epithelial cells in a dose-dependent manner. Butein also inhibited the protein and mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-stimulated A549 human lung epithelial cells in a dose-dependent manner. Butein inhibited TNF-α-induced reactive oxygen species (ROS) generation and nuclear factor-κB (NF-κB) activation in A549 cells; it also inhibited the phosphorylation of MAPKs and Akt, suggesting that the MAPK/Akt signaling pathway may be involved in the butein-mediated inhibition of TNF-α-induced leukocyte adhesion to A549 cells. Collectively, our results suggest that butein affects cell adhesion through the inhibition of TNF-α-induced ICAM-1 and VCAM-1 expression by inhibiting the NF-κB/MAPK/Akt signaling pathway and ROS generation, thereby, elucidating the role of butein in the anti-inflammatory response.

  2. Palladium-Based Nanomaterials: A Platform to Produce Reactive Oxygen Species for Catalyzing Oxidation Reactions.

    PubMed

    Long, Ran; Huang, Hao; Li, Yaping; Song, Li; Xiong, Yujie

    2015-11-25

    Oxidation reactions by molecular oxygen (O2 ) over palladium (Pd)-based nanomaterials are a series of processes crucial to the synthesis of fine chemicals. In the past decades, investigations of related catalytic materials have mainly been focused on the synthesis of Pd-based nanomaterials from the angle of tailoring their surface structures, compositions and supporting materials, in efforts to improve their activities in organic reactions. From the perspective of rational materials design, it is imperative to address the fundamental issues associated with catalyst performance, one of which should be oxygen activation by Pd-based nanomaterials. Here, the fundamentals that account for the transformation from O2 to reactive oxygen species over Pd, with a focus on singlet O2 and its analogue, are introduced. Methods for detecting and differentiating species are also presented to facilitate future fundamental research. Key factors for tuning the oxygen activation efficiencies of catalytic materials are then outlined, and recent developments in Pd-catalyzed oxygen-related organic reactions are summarized in alignment with each key factor. To close, we discuss the challenges and opportunities for photocatalysis research at this unique intersection as well as the potential impact on other research fields.

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

    PubMed

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

    2017-04-10

    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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Bilirubin inhibits the up-regulation of inducible nitric oxide synthase by scavenging reactive oxygen species generated by the toll-like receptor 4-dependent activation of NADPH oxidase.

    PubMed

    Idelman, Gila; Smith, Darcey L H; Zucker, Stephen D

    2015-08-01

    It has been previously shown that bilirubin prevents the up-regulation of inducible nitric oxide synthase (iNOS) in response to LPS. The present study examines whether this effect is exerted through modulation of Toll-Like Receptor-4 (TLR4) signaling. LPS-stimulated iNOS and NADPH oxidase (Nox) activity in RAW 264.7 murine macrophages was assessed by measuring cellular nitrate and superoxide ( [Formula: see text] ) production, respectively. The generation of both nitrate and [Formula: see text] in response to LPS was suppressed by TLR4 inhibitors, indicating that activation of iNOS and Nox is TLR4-dependent. While treatment with superoxide dismutase (SOD) and bilirubin effectively abolished LPS-mediated [Formula: see text] production, hydrogen peroxide and nitrate release were inhibited by bilirubin and PEG-catalase, but not SOD, supporting that iNOS activation is primarily dependent upon intracellular H2O2. LPS treatment increased nuclear translocation of the redox-sensitive transcription factor Hypoxia Inducible Factor-1α (HIF-1α), an effect that was abolished by bilirubin. Cells transfected with murine iNOS reporter constructs in which the HIF-1α-specific hypoxia response element was disrupted exhibited a blunted response to LPS, supporting that HIF-1α mediates Nox-dependent iNOS expression. Bilirubin, but not SOD, blocked the cellular production of interferon-β, while interleukin-6 production remained unaffected. These data support that bilirubin inhibits the TLR4-mediated up-regulation of iNOS by preventing activation of HIF-1α through scavenging of Nox-derived reactive oxygen species. Bilirubin also suppresses interferon-β release via a ROS-independent mechanism. These findings characterize potential mechanisms for the anti-inflammatory effects of bilirubin.

  11. 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.

  12. DNA cleavage activity of Fe(II)N4Py under photo irradiation in the presence of 1,8-naphthalimide and 9-aminoacridine: unexpected effects of reactive oxygen species scavengers.

    PubMed

    Li, Qian; Browne, Wesley R; Roelfes, Gerard

    2011-09-05

    The DNA cleavage activity of the iron(II) complex of the ligand N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine (N4Py) was investigated in the presence of the chromophores 1,8-naphthalimide (NI) and 9-aminoacridine (AA) under photo irradiation at 355 and 400.8 nm and compared to the activity of the complex without the chromophores. Whereas in most cases no synergistic effect of the added chromophores on DNA cleavage efficiency was observed, it was found that for Fe(II)N4Py, in combination with NI under irradiation at 355 nm, the DNA cleavage activity was increased. Surprisingly, it was found that the addition of reactive oxygen species (ROS) scavengers gave rise to significantly increased DNA cleavage efficiency, which is a highly counterintuitive observation since ROS are needed to achieve DNA cleavage. A hypothesis is put forward to explain, at least partly, these results. It is proposed that the addition of scavengers inhibits quenching of (3)NI*, thus making photo-induced electron transfer between (3)NI* and Fe(III)N4Py more efficient. This results in reduction of Fe(III)N4Py to Fe(II)N4Py, which can then react with ROS giving rise to DNA cleavage. Hence the role of the scavengers is to maintain a close to optimal concentration of ROS. The present study serves as an illustration of the care that needs to be exercised in interpreting the results of experiments using standard ROS scavengers, since especially in complex systems such as presented here they can give rise to unexpected phenomena. In the presence of 1,8-naphthalimide or 9-aminoacridine, ROS scavengers can increase the DNA cleavage efficiency of Fe(II)N4Py complex under photo irradiation.

  13. Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by cross-linking of CD70 is dependent upon generation of reactive oxygen species and activation of p38 MAPK and JNK pathway.

    PubMed

    Park, Ga Bin; Kim, Yeong Seok; Lee, Hyun-Kyung; Song, Hyunkeun; Cho, Dae-Ho; Lee, Wang Jae; Hur, Dae Young

    2010-12-15

    CD70 is expressed in normal activated immune cells as well as in several types of tumors. It has been established that anti-CD70 mAb induces complement-dependent death of CD70(+) tumor cells, but how anti-CD70 mAb affects the intrinsic signaling is poorly defined. In this report, we show that ligation of CD70 expressed on EBV-transformed B cells using anti-CD70 mAb induced production of reactive oxygen species (ROS) and subsequent apoptosis. We observed an early expression of endoplasmic reticulum (ER) stress response genes that preceded the release of apoptotic molecules from the mitochondria and the cleavage of caspases. CD70-induced apoptosis was inhibited by pretreatment with the ER stress inhibitor salubrinal, ROS quencher N-acetylcysteine, and Ca(2+) chelator BAPTA. We supposed that ROS generation might be the first event of CD70-induced apoptosis because N-acetylcysteine blocked increases of ROS and Ca(2+), but BAPTA did not block ROS generation. We also found that CD70 stimulation activated JNK and p38 MAPK. JNK inhibitor SP600125 and p38 inhibitor SB203580 effectively blocked upregulation of ER stress-related genes and cleavage of caspases. Inhibition of ROS generation completely blocked phosphorylation of JNK and p38 MAPK and induction of ER stress-related genes. Taken together, we concluded that cross-linking of CD70 on EBV-transformed B cells triggered ER stress-mediated apoptosis via ROS generation and JNK and p38 MAPK pathway activation. Our report reveals alternate mechanisms of direct apoptosis through CD70 signaling and provides data supporting CD70 as a viable target for an Ab-based therapy against EBV-related tumors.

  14. 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

  15. 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

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

    PubMed Central

    Hyman, Lynne M.; Franz, Katherine J.

    2013-01-01

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

  17. 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.

  18. 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

  19. 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

  20. [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.

  1. 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

  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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. PsMPK7, a stress-associated mitogen-activated protein kinase (MAPK) in Phytophthora sojae, is required for stress tolerance, reactive oxygenated species detoxification, cyst germination, sexual reproduction and infection of soybean.

    PubMed

    Gao, Jian; Cao, Mingna; Ye, Wenwu; Li, Haiyang; Kong, Liang; Zheng, Xiaobo; Wang, Yuanchao

    2015-01-01

    The sensing of stress signals and their transduction into appropriate responses are crucial for the adaptation, survival and infection of phytopathogenic fungi and oomycetes. Amongst evolutionarily conserved pathways, mitogen-activated protein kinase (MAPK) cascades function as key signal transducers that use phosphorylation to convey information. In this study, we identified a gene, designated PsMPK7, one of 14 predicted genes encoding MAPKs in Phytophthora sojae. PsMPK7 was highly transcribed in each tested stage, but was up-regulated in the zoospore, cyst and cyst germination stages. Silencing of PsMPK7 affected the growth of germinated cysts, oospore production and the pathogenicity of soybean. PsMPK7 transcription was induced by stresses from sorbitol, NaCl and hydrogen peroxide. Transformants in which PsMPK7 expression was silenced (PsMPK7-silenced) were significantly more sensitive to osmotic and oxidative stress. Aniline blue and diaminobenzidine staining revealed that the silenced lines did not suppress the host reactive oxygen species (ROS) burst, indicating that either the inoculated plants activated stronger defence responses to the transformants and/or the PsMPK7-silenced transformants failed to overcome plant defences. In addition, extracellular secretion of laccase decreased in the silenced lines. Overall, our results indicate that the PsMPK7 gene encodes a stress-associated MAPK in P. sojae that is important not only for responses to various stresses, but also for ROS detoxification, cyst germination, sexual oospore production and infection of soybean.

  8. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

    PubMed

    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible.

  9. Biochar activated by oxygen plasma for supercapacitors

    NASA Astrophysics Data System (ADS)

    Gupta, Rakesh Kumar; Dubey, Mukul; Kharel, Parashu; Gu, Zhengrong; Fan, Qi Hua

    2015-01-01

    Biochar, also known as black carbon, is a byproduct of biomass pyrolysis. As a low-cost, environmental-friendly material, biochar has the potential to replace more expensive synthesized carbon nanomaterials (e.g. carbon nanotubes) for use in future supercapacitors. To achieve high capacitance, biochar requires proper activation. A conventional approach involves mixing biochar with a strong base and baking at a high temperature. However, this process is time consuming and energy inefficient (requiring temperatures >900 °C). This work demonstrates a low-temperature (<150 °C) plasma treatment that efficiently activates a yellow pine biochar. Particularly, the effects of oxygen plasma on the biochar microstructure and supercapacitor characteristics are studied. Significant enhancement of the capacitance is achieved: 171.4 F g-1 for a 5-min oxygen plasma activation, in comparison to 99.5 F g-1 for a conventional chemical activation and 60.4 F g-1 for untreated biochar. This enhancement of the charge storage capacity is attributed to the creation of a broad distribution in pore size and a larger surface area. The plasma activation mechanisms in terms of the evolution of the biochar surface and microstructure are further discussed.

  10. Cytochrome P450 Reductase: A Harbinger of Diffusible Reduced Oxygen Species

    PubMed Central

    Manoj, Kelath Murali; Gade, Sudeep Kumar; Mathew, Lazar

    2010-01-01

    The bi-enzymatic system of cytochrome P450 (CYP, a hemoprotein) and cytochrome P450 reductase (CPR, a diflavoenzyme) mediate the redox metabolism of diverse indigenous and xenobiotic molecules in various cellular and organ systems, using oxygen and NADPH. Curiously, when a 1∶1 ratio is seen to be optimal for metabolism, the ubiquitous CYP:CPR distribution ratio is 10 to 100∶1 or higher. Further, the NADPH equivalents consumed in these in vitro or in situ assemblies usually far exceeded the amount of substrate metabolized. We aimed to find the rationale to explain for these two oddities. We report here that CPR is capable of activating molecular oxygen on its own merit, generating diffusible reduced oxygen species (DROS). Also, in the first instance for a flavoprotein, CPR is shown to deplete peroxide via diffusible radical mediated process, thereby leading to the formation of water (but without significant evolution of oxygen). We also quantitatively demonstrate that the rate of oxygen activation and peroxide depletion by CPR accounts for the major reactivity in the CYP+CPR mixture. We show unambiguously that CPR is able to regulate the concentration of diffusible reduced oxygen species in the reaction milieu. These findings point out that CPR mediated processes are bound to be energetically ‘wasteful’ and potentially ‘hazardous’ owing to the unavoidable nature of the CPR to generate and deplete DROS. Hence, we can understand that CPR is distributed at low densities in cells. Some of the activities that were primarily attributed to the heme-center of CYP are now established to be a facet of the flavins of CPR. The current approach of modeling drugs to minimize “uncoupling” on the basis of erstwhile hypothesis stands questionable, considering the ideas brought forth in this work. PMID:20967245

  11. Cross-linking of B7-H1 on EBV-transformed B cells induces apoptosis through reactive oxygen species production, JNK signaling activation, and fasL expression.

    PubMed

    Kim, Yeong Seok; Park, Ga Bin; Lee, Hyun-Kyung; Song, Hyunkeun; Choi, In-Hak; Lee, Wang Jae; Hur, Dae Young

    2008-11-01

    B7-H1 is a newly identified member of the B7 family with important regulatory functions in cell-mediated immune responses, and it is expressed in human immune cells and several tumors. We first observed that expression of surface B7-H1 on B cells was increased during the immortalization process by EBV, which is strongly related to both inflammation and tumorigenesis. Cross-linking of B7-H1 on EBV-transformed B cells using anti-B7-H1 Ab (clone 130002) induced reactive oxygen species (ROS) generation, mitochondrial disruption, release of apoptotic proteins from mitochondria, and subsequent apoptosis. Inhibition of caspases and ROS generation recovered B7-H1-mediated apoptosis and proteolytic activities of caspase-8, -9, and -3. We observed that B7-H1 stimulation induced both transcription and translation of fasL. ZB4, an antagonistic anti-fas Ab, and NOK-1, an antagonistic anti-fasL Ab, effectively blocked apoptosis without exerting any influence on ROS generation. N-acetylcysteine (NAC) completely blocked the induction of fasL mRNA and protein. We found that B7-H1 stimulation activated the phosphorylation of JNK and c-jun and down-regulated ERK1/2 and p-Akt. NAC blocked the activation of JNK and down-regulation of ERK, but both z-VAD-fmk (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) and ZB4 did not inhibit JNK activation of B7-H1 stimulation. SP600125 blocked fasL induction and apoptosis but did not affect ROS generation after B7-H1 stimulation. Taken together, we concluded that B7-H1-mediated apoptosis on EBV-transformed B cells may be involved in the induction of fasL, which is evoked by ROS generation and JNK activation after cross-linking of B7-H1. These results provide a new concept for understanding reverse signaling through B7-H1 and another mechanism of tumor immunotherapy using anti-B7-H1.

  12. 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.

  13. [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.

  14. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology

    PubMed Central

    Oliveira, Matheus P.; Correa Soares, Juliana B. R.; Oliveira, Marcus F.

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  15. Dynamin 2 and c-Abl are novel regulators of hyperoxia-mediated NADPH oxidase activation and reactive oxygen species production in caveolin-enriched microdomains of the endothelium.

    PubMed

    Singleton, Patrick A; Pendyala, Srikanth; Gorshkova, Irina A; Mambetsariev, Nurbek; Moitra, Jaideep; Garcia, Joe G N; Natarajan, Viswanathan

    2009-12-11

    Reactive oxygen species (ROS) generation, particularly by the endothelial NADPH oxidase family of proteins, plays a major role in the pathophysiology associated with lung inflammation, ischemia/reperfusion injury, sepsis, hyperoxia, and ventilator-associated lung injury. We examined potential regulators of ROS production and discovered that hyperoxia treatment of human pulmonary artery endothelial cells induced recruitment of the vesicular regulator, dynamin 2, the non-receptor tyrosine kinase, c-Abl, and the NADPH oxidase subunit, p47(phox), to caveolin-enriched microdomains (CEMs). Silencing caveolin-1 (which blocks CEM formation) and/or c-Abl expression with small interference RNA inhibited hyperoxia-mediated tyrosine phosphorylation and association of dynamin 2 with p47(phox) and ROS production. In addition, treatment of human pulmonary artery endothelial cells with dynamin 2 small interfering RNA or the dynamin GTPase inhibitor, Dynasore, attenuated hyperoxia-mediated ROS production and p47(phox) recruitment to CEMs. Using purified recombinant proteins, we observed that c-Abl tyrosine-phosphorylated dynamin 2, and this phosphorylation increased p47(phox)/dynamin 2 association (change in the dissociation constant (K(d)) from 85.8 to 6.9 nm). Furthermore, exposure of mice to hyperoxia increased ROS production, c-Abl activation, dynamin 2 association with p47(phox), and pulmonary leak, events that were attenuated in the caveolin-1 knock-out mouse confirming a role for CEMs in ROS generation. These results suggest that hyperoxia induces c-Abl-mediated dynamin 2 phosphorylation required for recruitment of p47(phox) to CEMs and subsequent ROS production in lung endothelium.

  16. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Support nanostructure boosts oxygen transfer to catalytically active platinum nanoparticles.

    PubMed

    Vayssilov, Georgi N; Lykhach, Yaroslava; Migani, Annapaola; Staudt, Thorsten; Petrova, Galina P; Tsud, Nataliya; Skála, Tomáš; Bruix, Albert; Illas, Francesc; Prince, Kevin C; Matolín, Vladimír; Neyman, Konstantin M; Libuda, Jörg

    2011-04-01

    Interactions of metal particles with oxide supports can radically enhance the performance of supported catalysts. At the microscopic level, the details of such metal-oxide interactions usually remain obscure. This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts: (1) electron transfer from the Pt nanoparticle to the support, and (2) oxygen transfer from ceria to Pt. The electron transfer is favourable on ceria supports, irrespective of their morphology. Remarkably, the oxygen transfer is shown to require the presence of nanostructured ceria in close contact with Pt and, thus, is inherently a nanoscale effect. Our findings enable us to detail the formation mechanism of the catalytically indispensable Pt-O species on ceria and to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general.

  10. Arginine deiminase modulates endothelial tip cells via excessive synthesis of reactive oxygen species.

    PubMed

    Zhuo, Wei; Song, Xiaomin; Zhou, Hao; Luo, Yongzhang

    2011-10-01

    ADI (arginine deiminase), an enzyme that hydrolyses arginine, has been reported as an anti-angiogenesis agent. However, its molecular mechanism is unclear. We have demonstrated for the first time that ADI modulates the angiogenic activity of endothelial tip cells. By arginine depletion, ADI disturbs actin filament in endothelial tip cells, causing disordered migratory direction and decreased migration ability. Furthermore, ADI induces excessive synthesis of ROS (reactive oxygen species), and activates caspase 8-, but not caspase 9-, dependent apoptosis in endothelial cells. These findings provide a novel mechanism by which ADI inhibits tumour angiogenesis through modulating endothelial tip cells.

  11. [Ways of realizing apoptosis of human lymphocytes induced by UV-light and reactive oxygen species].

    PubMed

    Artiukhov, V G; Trubitsyna, M S; Nakvasina, M A; Solov'eva, E V; Lidokhova, O V

    2011-01-01

    Changes of DNA structural condition, the level of membrane Fas-receptor expression, caspase-3 functional activity, concentrations of Ca2+, p53 and cytochrome c proteins of human lymphocytes in dynamics of apoptosis development induced by UV-light (240-390 nm) at doses 151, 1510, 3020 J/m2 and reactive oxygen species (superoxide anion-radical, hydroxyl radicals, hydrogen peroxide, singlet oxygen) have been studied. UV-light and reactive oxygen species have been established to induce fragmentation of lymphocyte DNA after 20 h incubation of the modified cells. It has been shown, that the increase in the expression level of membrane death Fas-receptors is observed during 1-5 h after exposure oflymphocytes to UV-light and ROS compared with intact cells. Also revealed is augmentation of lymphocyte caspase-3 functional activity 4 h after generation of singlet oxygen, hydroxyl radical and hydrogen peroxide addition, as well as 8 and 24 and 6 and 8 h after UV-irradiation of the cells at doses 151 and 1510 J/m2, correspondingly. Using DNA-comet method made it possible to tape that DNA damages (single-strand breaks) appear 15-20 min after lymphocyte UV-irradiation at doses 1510 and 3020 J/m and addition of hydrogen peroxide in concentration 10(-6) mol/l (C1 type comet) and reach their maximum 6 h after modification of the cells (C2 and C3 type comets). It has been observed, that 6 h after exposure oflymphocytes to hydrogen peroxide and UV-light at doses 1510 and 3020 J/m2, the p53 level of investigated cells raises. It has also been shown that the higher level of calcium in lymphocyte cytosol in conditions of UV-light exposure (1510 J/m2) and exogenous generation of reactive oxygen species is caused by Ca2+ exit from intracellular depots as a result of activating the components of the phosphoinositide mechanism for transferring information into a cell. Ideas about correlation between alterations of the calcium level and initiation of programmed cellular destruction of human

  12. 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

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

    PubMed Central

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

    2013-01-01

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

  14. 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.

  15. 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.

  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. 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

  18. 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.

  19. 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

  20. 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.

  1. Cell death induced by direct laser activation of singlet oxygen at 1270 nm

    NASA Astrophysics Data System (ADS)

    Anquez, F.; El Yazidi Belkoura, I.; Suret, P.; Randoux, S.; Courtade, E.

    2013-02-01

    Singlet oxygen plays a major role in many chemical and biological photo-oxidation processes. It has a high chemical reactivity, which is commonly harnessed for therapeutic issues. Indeed, singlet oxygen is recognized as the major cytotoxic agent in photodynamic therapy. In this treatment of cancer, singlet oxygen is created, among other reactive species, by an indirect transfer of energy from light to molecular oxygen via excitation of a photosensitizer. In this paper, we show that the conventional singlet oxygen production scheme can be simplified. Production of singlet oxygen is achieved in living cells from photosensitizer-free 1270 nm laser excitation of the electronic ground state of molecular oxygen. The quantity of singlet oxygen produced in this way is sufficient to induce an oxidative stress leading to cell death. Other effects such as thermal stress are discriminated, and we conclude that cell death is only due to singlet oxygen creation. This new simplified scheme of singlet oxygen activation can be seen as a breakthrough for phototherapies of malignant diseases and/or as a non-invasive possibility to generate reactive oxygen species in a tightly controlled manner.

  2. The Quantum Biology of Reactive Oxygen Species Partitioning Impacts Cellular Bioenergetics

    NASA Astrophysics Data System (ADS)

    Usselman, Robert J.; Chavarriaga, Cristina; Castello, Pablo R.; Procopio, Maria; Ritz, Thorsten; Dratz, Edward A.; Singel, David J.; Martino, Carlos F.

    2016-12-01

    Quantum biology is the study of quantum effects on biochemical mechanisms and biological function. We show that the biological production of reactive oxygen species (ROS) in live cells can be influenced by coherent electron spin dynamics, providing a new example of quantum biology in cellular regulation. ROS partitioning appears to be mediated during the activation of molecular oxygen (O2) by reduced flavoenzymes, forming spin-correlated radical pairs (RPs). We find that oscillating magnetic fields at Zeeman resonance alter relative yields of cellular superoxide (O2•‑) and hydrogen peroxide (H2O2) ROS products, indicating coherent singlet-triplet mixing at the point of ROS formation. Furthermore, the orientation-dependence of magnetic stimulation, which leads to specific changes in ROS levels, increases either mitochondrial respiration and glycolysis rates. Our results reveal quantum effects in live cell cultures that bridge atomic and cellular levels by connecting ROS partitioning to cellular bioenergetics.

  3. The Quantum Biology of Reactive Oxygen Species Partitioning Impacts Cellular Bioenergetics

    PubMed Central

    Usselman, Robert J.; Chavarriaga, Cristina; Castello, Pablo R.; Procopio, Maria; Ritz, Thorsten; Dratz, Edward A.; Singel, David J.; Martino, Carlos F.

    2016-01-01

    Quantum biology is the study of quantum effects on biochemical mechanisms and biological function. We show that the biological production of reactive oxygen species (ROS) in live cells can be influenced by coherent electron spin dynamics, providing a new example of quantum biology in cellular regulation. ROS partitioning appears to be mediated during the activation of molecular oxygen (O2) by reduced flavoenzymes, forming spin-correlated radical pairs (RPs). We find that oscillating magnetic fields at Zeeman resonance alter relative yields of cellular superoxide (O2•−) and hydrogen peroxide (H2O2) ROS products, indicating coherent singlet-triplet mixing at the point of ROS formation. Furthermore, the orientation-dependence of magnetic stimulation, which leads to specific changes in ROS levels, increases either mitochondrial respiration and glycolysis rates. Our results reveal quantum effects in live cell cultures that bridge atomic and cellular levels by connecting ROS partitioning to cellular bioenergetics. PMID:27995996

  4. 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.

  5. Surface Electrochemistry of Chloro(phthalocyaninato)rhodium(III) species, and Oxygen Reduction Electrocatalysis, Formation of a Dimeric Species

    DTIC Science & Technology

    1991-08-20

    rhodium(III) Species, and Oxygen Reduction Electrocatalysis , Formation of a Dimeric Species By Y.-H. Tse, P. Seymour, N. Kobayashi, H. Lam, C.C. Leznoff... Electrocatalysis , Formation of a Dimeric Species 12. PERSONAL AuTI𔃾OR(S)* Y.-H. Ise, P. Sey;mour, N. Kobayashi, H. Lam, C.C. Leznoff, and A.B.P. L...Oxygen Reduction Electrocatalysis . Formation of a Dimeric Species. Yu-Hong Tse, Penny Seymour, Nagao Kobayashi, 1 Herman Lam, Clifford C. Leznoff. and

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

    PubMed

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

    2014-01-01

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

  7. 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

  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. Influence of lightweight ambulatory oxygen on oxygen use and activity patterns of COPD patients receiving long-term oxygen therapy.

    PubMed

    Casaburi, Richard; Porszasz, Janos; Hecht, Ariel; Tiep, Brian; Albert, Richard K; Anthonisen, Nicholas R; Bailey, William C; Connett, John E; Cooper, J Allen; Criner, Gerard J; Curtis, Jeffrey; Dransfield, Mark; Lazarus, Stephen C; Make, Barry; Martinez, Fernando J; McEvoy, Charlene; Niewoehner, Dennis E; Reilly, John J; Scanlon, Paul; Scharf, Steven M; Sciurba, Frank C; Woodruff, Prescott

    2012-02-01

    Lightweight ambulatory oxygen devices are provided on the assumptions that they enhance compliance and increase activity, but data to support these assumptions are lacking. We studied 22 patients with severe chronic obstructive pulmonary disease receiving long-term oxygen therapy (14 men, average age = 66.9 y, FEV(1) = 33.6%pred, PaO(2) at rest = 51.7 torr) who were using E-cylinders as their portable oxygen. Subjects were recruited at 5 sites and studied over a 2-week baseline period and for 6 months after randomizing them to either continuing to use 22-lb E-cylinders towed on a cart or to carrying 3.6-lb aluminum cylinders. Utilizing novel electronic devices, ambulatory and stationary oxygen use was monitored continuously over the 2 weeks prior to and the 6 months following randomization. Subjects wore tri-axial accelerometers to monitor physical activity during waking hours for 2-3 weeks prior to, and at 3 and 6 months after, randomization. Seventeen subjects completed the study. At baseline, subjects used 17.2 hours of stationary and 2.5 hours of ambulatory oxygen daily. At 6 months, ambulatory oxygen use was 1.4 ± 1.0 hrs in those randomized to E-cylinders and 1.9 ± 2.4 hrs in those using lightweight oxygen (P = NS). Activity monitoring revealed low activity levels prior to randomization and no significant increase over time in either group. In this group of severe chronic obstructive pulmonary disease patients, providing lightweight ambulatory oxygen did not increase either oxygen use or activity. Future efforts might focus on strategies to encourage oxygen use and enhance activity in this patient group. This trial is registered at ClinicalTrials.gov (NCT003257540).

  10. Cerebral Oxygen Delivery and Consumption During Evoked Neural Activity

    PubMed Central

    Vazquez, Alberto L.; Masamoto, Kazuto; Fukuda, Mitsuhiro; Kim, Seong-Gi

    2010-01-01

    Increases in neural activity evoke increases in the delivery and consumption of oxygen. Beyond observations of cerebral tissue and blood oxygen, the role and properties of cerebral oxygen delivery and consumption during changes in brain function are not well understood. This work overviews the current knowledge of functional oxygen delivery and consumption and introduces recent and preliminary findings to explore the mechanisms by which oxygen is delivered to tissue as well as the temporal dynamics of oxygen metabolism. Vascular oxygen tension measurements have shown that a relatively large amount of oxygen exits pial arterioles prior to capillaries. Additionally, increases in cerebral blood flow (CBF) induced by evoked neural activation are accompanied by arterial vasodilation and also by increases in arteriolar oxygenation. This increase contributes not only to the down-stream delivery of oxygen to tissue, but also to delivery of additional oxygen to extra-vascular spaces surrounding the arterioles. On the other hand, the changes in tissue oxygen tension due to functional increases in oxygen consumption have been investigated using a method to suppress the evoked CBF response. The functional decreases in tissue oxygen tension induced by increases in oxygen consumption are slow to evoked changes in CBF under control conditions. Preliminary findings obtained using flavoprotein autofluorescence imaging suggest cellular oxidative metabolism changes at a faster rate than the average changes in tissue oxygen. These issues are important in the determination of the dynamic changes in tissue oxygen metabolism from hemoglobin-based imaging techniques such as blood oxygenation-level dependent functional magnetic resonance imaging (fMRI). PMID:20616881

  11. Khz (fusion product of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis in human colon carcinoma HCT116 cells, accompanied by an increase in reactive oxygen species, activation of caspase 3, and increased intracellular Ca²⁺.

    PubMed

    Kim, Tae Hwan; Kim, Ju Sung; Kim, Zoo Haye; Huang, Ren Bin; Chae, Young Lye; Wang, Ren Sheng

    2015-03-01

    Khz (a fusion mycelium of Ganoderma lucidum and Polyporus umbellatus mycelia) is isolated from ganoderic acid and P. umbellatus and it exerts antiproliferative effects against malignant cells. However, no previous study has reported the inhibitory effects of Khz on the growth of human colon cancer cells. In the present study, we found that Khz suppressed cell division and induced apoptosis in HCT116 cells. Khz cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Khz reduced cell viability and mitochondrial membrane potential levels and it also induced disruption of the mitochondrial membrane potential and increased calcium concentration and reactive oxygen species generation. Khz increased caspase 3, PARP, caspase 7, and caspase 9 levels, but reduced Bcl-2 protein levels. Flow cytometry showed that the percentage of HCT116 cells in the sub-G1 phase of the cell cycle increased in response to Khz treatment.

  12. 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

  13. 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

  14. Reactive oxygen species-mediated unfolded protein response pathways in preimplantation embryos

    PubMed Central

    Ali, Ihsan; Shah, Syed Zahid Ali; Jin, Yi; Li, Zhong-Shu; Ullah, Obaid

    2017-01-01

    Excessive production of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress-mediated responses are critical to embryonic development in the challenging in vitro environment. ROS production increases during early embryonic development with the increase in protein requirements for cell survival and growth. The ER is a multifunctional cellular organelle responsible for protein folding, modification, and cellular homeostasis. ER stress is activated by a variety of factors including ROS. Such stress leads to activation of the adaptive unfolded protein response (UPR), which restores homeostasis. However, chronic stress can exceed the toleration level of the ER, resulting in cellular apoptosis. In this review, we briefly describe the generation and impact of ROS in preimplantation embryo development, the ROS-mediated activation mechanism of the UPR via the ER, and the subsequent activation of signaling pathways following ER stress in preimplantation embryos. PMID:28057903

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

    PubMed

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

    2012-10-01

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

  16. A ligand field chemistry of oxygen generation by the oxygen-evolving complex and synthetic active sites.

    PubMed

    Betley, Theodore A; Surendranath, Yogesh; Childress, Montana V; Alliger, Glen E; Fu, Ross; Cummins, Christopher C; Nocera, Daniel G

    2008-03-27

    Oxygen-oxygen bond formation and O2 generation occur from the S4 state of the oxygen-evolving complex (OEC). Several mechanistic possibilities have been proposed for water oxidation, depending on the formal oxidation state of the Mn atoms. All fall under two general classifications: the AB mechanism in which nucleophilic oxygen (base, B) attacks electrophilic oxygen (acid, A) of the Mn4Ca cluster or the RC mechanism in which radical-like oxygen species couple within OEC. The critical intermediate in either mechanism involves a metal oxo, though the nature of this oxo for AB and RC mechanisms is disparate. In the case of the AB mechanism, assembly of an even-electron count, high-valent metal-oxo proximate to a hydroxide is needed whereas, in an RC mechanism, two odd-electron count, high-valent metal oxos are required. Thus the two mechanisms give rise to very different design criteria for functional models of the OEC active site. This discussion presents the electron counts and ligand geometries that support metal oxos for AB and RC O-O bond-forming reactions. The construction of architectures that bring two oxygen functionalities together under the purview of the AB and RC scenarios are described.

  17. 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.

  18. DNA evidence uncompromised by active oxygen.

    PubMed

    Castelló, Ana; Francés, Francesc; Verdú, Fernando

    2010-03-05

    Currently, forensic sciences can make use of the potential of instrumental analysis techniques to obtain information from the smallest, even invisible, samples. However, as laboratory techniques improve, so too should the procedures applied in the search for and initial testing of clues in order to be equally effective. This requires continuous revision so that those procedures may resolve the problems that samples present. As far as bloodstains are concerned, there are methods available that are recognized as being both highly sensitive and effective. Nevertheless, the marketing of new cleaning products, those that contain active oxygen, has raised doubts about the ability of those procedures to detect blood. It has been shown that stains washed with these detergents (and still visible) invalidated both the presumptive test (reduced phenolphthalein, luminol, and Bluestar) and that applied for determining human hemoglobin. These findings have caused considerable concern both within the forensic and scientific community, and among the general public, so obliging us to seek solutions. In this work, the effect of these new cleaning products on DNA analyses is studied. The results, encouraging ones, show that these detergents, despite invalidating all other tests, do not hinder the extraction, or the subsequent analysis, of DNA.

  19. 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.

  20. 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.

  1. Targeting and Regulation of Reactive Oxygen Species Generation by Nox Family NADPH Oxidases

    PubMed Central

    Morand, Stanislas; Hurt, Darrell; Ueyama, Takehiko

    2009-01-01

    Abstract Nox family NADPH oxidases serve a variety of functions requiring reactive oxygen species (ROS) generation, including antimicrobial defense, biosynthetic processes, oxygen sensing, and redox-based cellular signaling. We explored targeting, assembly, and activation of several Nox family oxidases, since ROS production appears to be regulated both spatially and temporally. Nox1 and Nox3 are similar to the phagocytic (Nox2-based) oxidase, functioning as multicomponent superoxide-generating enzymes. Factors regulating their activities include cytosolic activator and organizer proteins and GTP-Rac. Their regulation varies, with the following rank order: Nox2 > Nox1 > Nox3. Determinants of subcellular targeting include: (a) formation of Nox-p22phox heterodimeric complexes allowing plasma membrane translocation, (b) phospholipids-binding specificities of PX domain-containing organizer proteins (p47phox or Nox organizer 1 (Noxo1 and p40phox), and (c) variably splicing of Noxo1 PX domains directing them to nuclear or plasma membranes. Dual oxidases (Duox1 and Duox2) are targeted by different mechanisms. Plasma membrane targeting results in H2O2 release, not superoxide, to support extracellular peroxidases. Human Duox1 and Duox2 have no demonstrable peroxidase activity, despite their extensive homology with heme peroxidases. The dual oxidases were reconstituted by Duox activator 2 (Duoxa2) or two Duoxa1 variants, which dictate maturation, subcellular localization, and the type of ROS generated by forming stable complexes with Duox. Antioxid Redox Signal. 11, 2607–2619. PMID:19438290

  2. 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.

  3. The role of reactive oxygen species in the induction of Ty1 retrotransposition in Saccharomyces cerevisiae.

    PubMed

    Stoycheva, Teodora; Pesheva, Margarita; Venkov, Pencho

    2010-05-01

    Here we provide evidence for a dependence between the increased production of reactive oxygen species and the activation of Ty1 retrotransposition. We have found that the strong activator of Ty1 mobility, methylmethane sulphonate, can not induce Ty1 retrotransposition in cells with compromised mitochondrial oxidative phosphorylation (rho(-); sco1Delta), which is the major source for production of reactive oxygen species (ROS) in Saccharomyces cerevisiae. The quantitative estimation of superoxide anions in living cells showed that rho(+) cells exposed to methylmethane sulphonate increase Ty1 retrotransposition and superoxide levels. The increase of superoxide anions by the superoxide generator menadione is accompanied by induction of Ty1 mobility without any treatment with a DNA-damaging agent. Higher frequencies of retrotransposition were found in rho(+) and rho(-) cells treated with exogenously added hydrogen peroxide or in cells with disrupted YAP1 gene characterized by increased intracellular levels of hydrogen peroxide. These data indicate that increased levels of ROS may have an independent and key role in the induction of Ty1 retrotransposition.

  4. 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.

  5. Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: a possible role in atherosclerosis.

    PubMed

    Hseu, You-Cheng; Senthil Kumar, K J; Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun; Lin, Cheng-Wen; Lu, Fung-Jou; Yang, Hsin-Ling

    2014-01-15

    Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25-200μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE2 production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease.

  6. Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of nuclear factor-κB/activator protein-1 signaling pathways: A possible role in atherosclerosis

    SciTech Connect

    Hseu, You-Cheng; Senthil Kumar, K.J.; Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun; Lin, Cheng-Wen; Lu, Fung-Jou; Yang, Hsin-Ling

    2014-01-15

    Humic acid (HA) has been implicated as one of the etiological factors in the peripheral vasculopathy of blackfoot disease (BFD) in Taiwan. However, the underlying pathophysiological mechanisms of BFD are not well defined. In this study, we used an in vitro and in vivo model, in which HA (25–200 μg/mL) activated macrophages to produce pro-inflammatory molecules by activating their transcriptional factors. HA exposure induced NO and PGE{sub 2} production followed by induction of iNOS and COX-2 through NF-κB/AP-1 transactivation in macrophages. In addition, the production of TNF-α and IL-1β was significantly increased by HA. Moreover, HA-induced iNOS and COX-2 expression were down-regulated by the NF-κB and AP-1 inhibitors pyrrolidine dithiocarbamate (PDTC) and Tanshinone, respectively. Furthermore, generations of ROS and nitrotyrosine, as well as activation of the AKT and MAPKs signaling cascades were observed after HA exposure. Specifically, HA-induced NF-κB activation was mediated by ROS and AKT, and that HA-induced AP-1 activation was mediated by JNK and ERK. Notably, HA-mediated AKT, JNK, and ERK activation was ROS-independent. The inflammatory potential of HA was correlated with increased expression of HO-1 and Nrf2. Furthermore, an in vivo study confirms that mice exposed to HA, the serum levels of TNF-α and IL-1β was significantly increased in a dose-dependent manner. This report marks the first confirmation that environmental exposure of HA induces inflammation in macrophages, which may be one of the main causes of early atherogenesis in blackfoot disease. - Highlights: • Humic acid (HA) induce pro-inflammatory cytokines and mediators in macrophages. • HA-induced inflammation is mediated by ROS and NF-κB/AP-1 signaling pathways. • The inflammatory potential of HA correlated with activation of Nrf2/HO-1 genes. • HA exposure to mice increased pro-inflammatory cytokines production in vivo. • HA may be one of the main causes of early

  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. 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...

  9. Physiological levels of reactive oxygen species are required to maintain genomic stability in stem cells.

    PubMed

    Li, Tao-Sheng; Marbán, Eduardo

    2010-07-01

    Stem cell cytogenetic abnormalities constitute a roadblock to regenerative therapies. We investigated the possibility that reactive oxygen species (ROSs) influence genomic stability in cardiac and embryonic stem cells. Karyotypic abnormalities in primary human cardiac stem cells were suppressed by culture in physiological (5%) oxygen, but addition of antioxidants to the medium unexpectedly increased aneuploidy. Intracellular ROS levels were moderately decreased in physiological oxygen, but dramatically decreased by the addition of high-dose antioxidants. Quantification of DNA damage in cardiac stem cells and in human embryonic stem cells revealed a biphasic dose-dependence: antioxidants suppressed DNA damage at low concentrations, but potentiated such damage at higher concentrations. High-dose antioxidants decreased cellular levels of ATM (ataxia-telangiectasia mutated) and other DNA repair enzymes, providing a potential mechanistic basis for the observed effects. These results indicate that physiological levels of intracellular ROS are required to activate the DNA repair pathway for maintaining genomic stability in stem cells. The concept of an "oxidative optimum" for genomic stability has broad implications for stem cell biology and carcinogenesis.

  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. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

    PubMed

    Callaway, Danielle A; Jiang, Jean X

    2015-07-01

    Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

  12. 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.

  13. 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.

  14. Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture.

    PubMed

    López, E; Arce, C; Oset-Gasque, M J; Cañadas, S; González, M P

    2006-03-15

    Cadmium is a toxic agent that it is also an environmental contaminant. Cadmium exposure may be implicated in some humans disorders related to hyperactivity and increased aggressiveness. This study presents data indicating that cadmium induces cellular death in cortical neurons in culture. This death could be mediated by an apoptotic and a necrotic mechanism. The apoptotic death may be mediated by oxidative stress with reactive oxygen species (ROS) formation which could be induced by mitochondrial membrane dysfunction since this cation produces: (a) depletion of mitochondrial membrane potential and (b) diminution of ATP levels with ATP release. Necrotic death could be mediated by lipid peroxidation induced by cadmium through an indirect mechanism (ROS formation). On the other hand, 40% of the cells survive cadmium action. This survival seems to be mediated by the ability of these cells to activate antioxidant defense systems, since cadmium reduced the intracellular glutathione levels and induced catalase and SOD activation in these cells.

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

    PubMed

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

    2011-08-01

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

  16. Mitochondrial STAT3 and reactive oxygen species: A fulcrum of adipogenesis?

    PubMed Central

    Kramer, Adam H; Kadye, Rose; Houseman, Pascalene S; Prinsloo, Earl

    2015-01-01

    The balance between cellular lineages can be controlled by reactive oxygen species (ROS). Cellular differentiation into adipocytes is highly dependent on the production of ROS to initiate the process through activation of multiple interlinked factors that stimulate mitotic clonal expansion and cellular maturation. The signal transducer and activator of transcription family of signaling proteins have accepted roles in adipogenesis and associated lipogenesis. Non-canonical mitochondrial localization of STAT3 and other members of the STAT family however opens up new avenues for investigation of its role in the aforementioned processes. Following recent observations of differences in mitochondrially localized serine 727 phosphorylated STAT3 (mtSTAT3-pS727) in preadipocytes and adipocytes, here, we hypothesize and speculate further on the role of mitochondrial STAT3 in adipogenesis. PMID:27127727

  17. 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.

  18. 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

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

    PubMed

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

    2009-08-01

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

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

    SciTech Connect

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian

    2014-11-01

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

  1. Reactive oxygen species-dependent HSP90 protein cleavage participates in arsenical As{sup +3}- and MMA{sup +3}-induced apoptosis through inhibition of telomerase activity via JNK activation

    SciTech Connect

    Shen, S.-C.; Yang, L.-Y.; Lin, H.-Y.; Wu, C.-Y.; Su, T.-H.; Chen, Y.-C.

    2008-06-01

    The effects of six arsenic compounds including As{sup +3}, MMA{sup +3}, DMA{sup +3}, As{sup +5}, MMA{sup +5}, and DMA{sup +5} on the viability of NIH3T3 cells were examined. As{sup +3} and MMA{sup +3}, but not the others, exhibited significant cytotoxic effects in NIH3T3 cells through apoptosis induction. The apoptotic events such as DNA fragmentation and chromosome condensation induced by As{sup +3} and MMA{sup +3} were prevented by the addition of NAC and CAT, and induction of HO-1 gene expression in accordance with cleavage of the HSP90 protein, and suppression of telomerase activity were observed in NIH3T3 cells under As{sup +3} and MMA{sup +3} treatments. An increase in the intracellular peroxide level was examined in As{sup +3}- and MMA{sup +3}-treated NIH3T3 cells, and As{sup +3}- and MMA{sup +3}-induced apoptotic events were blocked by NAC, CAT, and DPI addition. HSP90 inhibitors, GA and RD, significantly attenuated the telomerase activity in NIH3T3 cells with an enhancement of As{sup +3}- and MMA{sup +3}-induced cytotoxicity. Suppression of JNKs significantly inhibited As{sup +3}- and MMA{sup +3}-induced apoptosis by blocking HSP90 protein cleavage and telomerase reduction in NIH3T3 cells. Furthermore, Hb, SnPP, and dexferosamine showed no effect against As{sup +3}- and MMA{sup +3}-induced apoptosis, and overexpression of HO-1 protein or inhibition of HO-1 protein expression did not affect the apoptosis induced by As{sup +3} or MMA{sup +3}. These data provide the first evidence to indicate that apoptosis induced by As{sup +3} and MMA{sup +3} is mediated by an ROS-dependent degradation of HSP90 protein and reduction of telomerase via JNK activation, and HO-1 induction might not be involved.

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

    PubMed

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

    2015-05-15

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

  3. Cell respiration and formation of reactive oxygen species: facts and artefacts.

    PubMed

    Nohl, H; Kozlov, A V; Gille, L; Staniek, K

    2003-12-01

    It is generally taken as an established fact that mitochondrial respiration is associated with the generation of small amounts of ROS (reactive oxygen species). There are many arguments supporting this side activity. A major argument is the particular physico-chemical configuration of dioxygen, which prevents the transfer of a pair of electrons. Instead, oxygen is reduced by the successive transfer of single electrons, necessarily leading to intermediates with odd electrons. The high rate of turnover of oxygen in the respiratory chain in combination with the existence of single-electron carriers supports the concept of mitochondria as the major cellular ROS generator. Experimental evidence on the ability of mitochondria to generate ROS was, however, based essentially on in vitro experiments with isolated mitochondria. A variety of structural and functional alterations associated with the removal of mitochondria from the cell, as well as the routinely applied ROS detection methods, may lead to artefactual deviation of odd electrons to dioxygen. We therefore checked these correlations in view of ROS formation, including the often reported effect of the membrane potential on the establishment of a redox couple with oxygen out of sequence. For this purpose we developed novel methods to prove the authenticity of mitochondria for ROS generation in the living cell. Based on our experiments, we can exclude spontaneous release of ROS from mitochondria. However, we describe conditions under which mitochondria can be transformed to mild ROS generators. The site of single-electron deviation to dioxygen was found to be ubiquinol interacting with the Rieske iron-sulphur protein and low-potential cytochrome b of the bc (1) complex.

  4. 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.

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

    PubMed

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

    2016-10-18

    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

  6. 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

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

    PubMed Central

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

    2012-01-01

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

  8. Study of the photochemically generated of oxygen species by fullerene photosensitized CoS{sub 2} nanocompounds

    SciTech Connect

    Meng, Ze-Da; Zhu, Lei; Ullah, Kefayat; Ye, Shu; Sun, Qian; Jang, Won Kweon; Oh, Won-Chun

    2014-01-01

    Graphical abstract: - Highlights: • Reactive oxygen species was detected through oxidation reaction from DPCI to DPCO. • Generated reactive oxygen species and hydroxyl radicals can be analysis by DPCI degradation. • C{sub 60} has good effect during the photo-degradation processes. • Photocatalytic activity attributed to photo-absorption effect by C{sub 60} and cooperative effect of CoS{sub 2}. - Abstract: Reactive oxygen species (ROS) can be produced by interactions between sunlight and light-absorbing substance in natural water environment and can completely destroy various organic pollutants in wastewaters. In this study, CoS{sub 2} and CoS{sub 2}–fullerene were irradiated by visible light respectively. The generation of reactive oxygen species were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). In comparison with the separate effects of CoS{sub 2} and fullerene nanoparticles, the photochemically effect of the fullerene photosensitized CoS{sub 2} composites is increased significantly due to the synergetic effect between the fullerene and the CoS{sub 2} nanoparticles.

  9. 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.

  10. Hypoxia-Dependent Reactive Oxygen Species Signaling in the Pulmonary Circulation: Focus on Ion Channels

    PubMed Central

    Veit, Florian; Pak, Oleg; Brandes, Ralf P.

    2015-01-01

    Abstract Significance: An acute lack of oxygen in the lung causes hypoxic pulmonary vasoconstriction, which optimizes gas exchange. In contrast, chronic hypoxia triggers a pathological vascular remodeling causing pulmonary hypertension, and ischemia can cause vascular damage culminating in lung edema. Recent Advances: Regulation of ion channel expression and gating by cellular redox state is a widely accepted mechanism; however, it remains a matter of debate whether an increase or a decrease in reactive oxygen species (ROS) occurs under hypoxic conditions. Ion channel redox regulation has been described in detail for some ion channels, such as Kv channels or TRPC6. However, in general, information on ion channel redox regulation remains scant. Critical Issues and Future Directions: In addition to the debate of increased versus decreased ROS production during hypoxia, we aim here at describing and deciphering why different oxidants, under different conditions, can cause both activation and inhibition of channel activity. While the upstream pathways affecting channel gating are often well described, we need a better understanding of redox protein modifications to be able to determine the complexity of ion channel redox regulation. Against this background, we summarize the current knowledge on hypoxia-induced ROS-mediated ion channel signaling in the pulmonary circulation. Antioxid. Redox Signal. 22, 537–552 PMID:25545236

  11. 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

  12. Induction of reactive oxygen species in marine phytoplankton under crude oil exposure.

    PubMed

    Ozhan, Koray; Zahraeifard, Sara; Smith, Aaron P; Bargu, Sibel

    2015-12-01

    Exposure of phytoplankton to the water-accommodated fraction of crude oil can elicit a number of stress responses, but the mechanisms that drive these responses are unclear. South Louisiana crude oil was selected to investigate its effects on population growth, chlorophyll a (Chl a) content, antioxidative defense, and lipid peroxidation, for the marine diatom, Ditylum brightwellii, and the dinoflagellate, Heterocapsa triquetra, in laboratory-based microcosm experiments. The transcript levels of several possible stress-responsive genes in D. brightwellii were also measured. The microalgae were exposed to crude oil for up to 96 h, and Chl a content, superoxide dismutase (SOD), the glutathione pool (GSH and GSSG), and lipid peroxidation content were analyzed. The cell growth of both phytoplankton species was inhibited with increasing crude oil concentrations. Crude oil exposure did not affect Chl a content significantly in cells. SOD activities showed similar responses in both species, being enhanced at 4- and 8-mg/L crude oil exposure. Only H. triquetra demonstrated enhanced activity in GSSG pool and lipid peroxidation at 8-mg/L crude oil exposure, suggesting that phytoplankton species have distinct physiological responses and tolerance levels to crude oil exposure. This study indicated the activation of reactive oxygen species (ROS) in phytoplankton under crude oil exposure; however, the progressive damage in cells is still unknown. Thus, ROS-related damage in nucleic acid, lipids, proteins, and DNA, due to crude oil exposure could be a worthwhile subject of study to better understand crude oil toxicity at the base of the food web.

  13. 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.

  14. Redox activity of surface oxygen anions in oxygen-deficient perovskite oxides during electrochemical reactions.

    PubMed

    Mueller, David N; Machala, Michael L; Bluhm, Hendrik; Chueh, William C

    2015-01-19

    Surface redox-active centres in transition-metal oxides play a key role in determining the efficacy of electrocatalysts. The extreme sensitivity of surface redox states to temperatures, to gas pressures and to electrochemical reaction conditions renders them difficult to investigate by conventional surface-science techniques. Here we report the direct observation of surface redox processes by surface-sensitive, operando X-ray absorption spectroscopy using thin-film iron and cobalt perovskite oxides as model electrodes for elevated-temperature oxygen incorporation and evolution reactions. In contrast to the conventional view that the transition metal cations are the dominant redox-active centres, we find that the oxygen anions near the surface are a significant redox partner to molecular oxygen due to the strong hybridization between oxygen 2p and transition metal 3d electronic states. We propose that a narrow electronic state of significant oxygen 2p character near the Fermi level exchanges electrons with the oxygen adsorbates. This result highlights the importance of surface anion-redox chemistry in oxygen-deficient transition-metal oxides.

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

    PubMed

    Granger, D Neil; Kvietys, Peter R

    2015-12-01

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

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

    PubMed Central

    Granger, D. Neil; Kvietys, Peter R.

    2015-01-01

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

  17. Probing Oxygen Activation Sites in Two Flavoprotein Oxidases Using Chloride as an Oxygen Surrogate

    SciTech Connect

    Kommoju, Phaneeswara-Rao; Chen, Zhi-wei; Bruckner, Robert C.; Mathews, F. Scott; Jorns, Marilyn Schuman

    2011-08-16

    A single basic residue above the si-face of the flavin ring is the site of oxygen activation in glucose oxidase (GOX) (His516) and monomeric sarcosine oxidase (MSOX) (Lys265). Crystal structures of both flavoenzymes exhibit a small pocket at the oxygen activation site that might provide a preorganized binding site for superoxide anion, an obligatory intermediate in the two-electron reduction of oxygen. Chloride binds at these polar oxygen activation sites, as judged by solution and structural studies. First, chloride forms spectrally detectable complexes with GOX and MSOX. The protonated form of His516 is required for tight binding of chloride to oxidized GOX and for rapid reaction of reduced GOX with oxygen. Formation of a binary MSOX-chloride complex requires Lys265 and is not observed with Lys265Met. Binding of chloride to MSOX does not affect the binding of a sarcosine analogue (MTA, methylthioactetate) above the re-face of the flavin ring. Definitive evidence is provided by crystal structures determined for a binary MSOX-chloride complex and a ternary MSOX-chloride-MTA complex. Chloride binds in the small pocket at a position otherwise occupied by a water molecule and forms hydrogen bonds to four ligands that are arranged in approximate tetrahedral geometry: Lys265:NZ, Arg49:NH1, and two water molecules, one of which is hydrogen bonded to FAD:N5. The results show that chloride (i) acts as an oxygen surrogate, (ii) is an effective probe of polar oxygen activation sites, and (iii) provides a valuable complementary tool to the xenon gas method that is used to map nonpolar oxygen-binding cavities.

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

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited α3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identify mROS as a putative homeostatic signalling molecule coupling cellular metabolism to the strength of inhibitory transmission.

  19. Protective mechanisms of helminths against reactive oxygen species are highly promising drug targets.

    PubMed

    Perbandt, Markus; Ndjonka, Dieudonne; Liebau, Eva

    2014-01-01

    Helminths that are the causative agents of numerous neglected tropical diseases continue to be a major problem for human global health. In the absence of vaccines, control relies solely on pharmacoprophylaxis and pharmacotherapy to reduce transmission and to relieve symptoms. There are only a few drugs available and resistance in helminths of lifestock has been observed to the same drugs that are also used to treat humans. Clearly there is an urgent need to find novel antiparasitic compounds. Not only are helminths confronted with their own metabolically derived toxic and redox-active byproducts but also with the production of reactive oxygen species (ROS) by the host immune system, adding to the overall oxidative burden of the parasite. Antioxidant enzymes of helminths have been identified as essential proteins, some of them biochemically distinct to their host counterpart and thus appealing drug targets. In this review we have selected a few enzymatic antioxidants of helminths that are thought to be druggable.

  20. Interaction of hyperlipidemia and reactive oxygen species: Insights from the lipid-raft platform

    PubMed Central

    Amiya, Eisuke

    2016-01-01

    Reactive oxygen species (ROS) and oxidative stress are closely associated with the development of atherosclerosis, and the most important regulator of ROS production in endothelial cells is NADPH oxidase. Activation of NADPH oxidase requires the assembly of multiple subunits into lipid rafts, which include specific lipid components, including free cholesterol and specific proteins. Disorders of lipid metabolism such as hyperlipidemia affect the cellular lipid components included in rafts, resulting in modification of cellular reactions that produce ROS. In the similar manner, several pathways associating ROS production are affected by the presence of lipid disorder through raft compartments. In this manuscript, we review the pathophysiological implications of hyperlipidemia and lipid rafts in the production of ROS. PMID:28070236

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

    PubMed

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

    2015-01-01

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

  2. Catalytic Coupling of Oxidative Phosphorylation, ATP Demand, and Reactive Oxygen Species Generation

    PubMed Central

    Bazil, Jason N.; Beard, Daniel A.; Vinnakota, Kalyan C.

    2016-01-01

    Competing models of mitochondrial energy metabolism in the heart are highly disputed. In addition, the mechanisms of reactive oxygen species (ROS) production and scavenging are not well understood. To deepen our understanding of these processes, a computer model was developed to integrate the biophysical processes of oxidative phosphorylation and ROS generation. The model was calibrated with experimental data obtained from isolated rat heart mitochondria subjected to physiological conditions and workloads. Model simulations show that changes in the quinone pool redox state are responsible for the apparent inorganic phosphate activation of complex III. Model simulations predict that complex III is responsible for more ROS production during physiological working conditions relative to complex I. However, this relationship is reversed under pathological conditions. Finally, model analysis reveals how a highly reduced quinone pool caused by elevated levels of succinate is likely responsible for the burst of ROS seen during reperfusion after ischemia. PMID:26910433

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

    PubMed Central

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

    2016-01-01

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

  4. Targeted interception of signaling reactive oxygen species in the vascular endothelium

    PubMed Central

    Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2017-01-01

    Reactive oxygen species (ROS) are implicated as injurious and as signaling agents in human maladies including inflammation, hyperoxia, ischemia-reperfusion and acute lung injury. ROS produced by the endothelium play an important role in vascular pathology. They quench, for example, nitric oxide, and mediate pro-inflammatory signaling. Antioxidant interventions targeted for the vascular endothelium may help to control these mechanisms. Animal studies have demonstrated superiority of targeting ROS-quenching enzymes catalase and superoxide dismutase to endothelial cells over nontargeted formulations. A diverse arsenal of targeted antioxidant formulations devised in the last decade shows promising results for specific quenching of endothelial ROS. In addition to alleviation of toxic effects of excessive ROS, these targeted interventions suppress pro-inflammatory mechanisms, including endothelial cytokine activation and barrier disruption. These interventions may prove useful in experimental biomedicine and, perhaps, in translational medicine. PMID:22834201

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

    SciTech Connect

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

    2006-03-10

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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Cross-talk of nitric oxide and reactive oxygen species in plant programed cell death

    PubMed Central

    Wang, Yiqin; Loake, Gary J.; Chu, Chengcai

    2013-01-01

    In plants, programed cell death (PCD) is an important mechanism to regulate multiple aspects of growth and development, as well as to remove damaged or infected cells during responses to environmental stresses and pathogen attacks. Under biotic and abiotic stresses, plant cells exhibit a rapid synthesis of nitric oxide (NO) and a parallel accumulation of reactive oxygen species (ROS). Frequently, these responses trigger a PCD process leading to an intrinsic execution of plant cells. The accumulating evidence suggests that both NO and ROS play key roles in PCD. These redox active small molecules can trigger cell death either independently or synergistically. Here we summarize the recent progress on the cross-talk of NO and ROS signals in the hypersensitive response, leaf senescence, and other kinds of plant PCD caused by diverse cues. PMID:23967004

  11. 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.

  12. A role for reactive oxygen species in the antibacterial properties of carbon monoxide-releasing molecules.

    PubMed

    Tavares, Ana Filipa N; Nobre, Lígia S; Saraiva, Lígia M

    2012-11-01

    Carbon monoxide-releasing molecules (CO-RMs) are, in general, transition metal carbonyl complexes that liberate controlled amounts of CO. In animal models, CO-RMs have been shown to reduce myocardial ischaemia, inflammation and vascular dysfunction, and to provide a protective effect in organ transplantation. Moreover, CO-RMs are bactericides that kill both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Herein are reviewed the microbial genetic and biochemical responses associated with CO-RM-mediated cell death. Particular emphasis is given to the data revealing that CO-RMs induce the generation of reactive oxygen species (ROS), which contribute to the antibacterial activity of these compounds.

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

    PubMed Central

    Liu, Rui-Ming; Desai, Leena P.

    2015-01-01

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

  14. 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.

  15. Evaluation of fatty acid oxidation by reactive oxygen species induced in liquids using atmospheric-pressure nonthermal plasma jets

    NASA Astrophysics Data System (ADS)

    Tani, Atsushi; Fukui, Satoshi; Ikawa, Satoshi; Kitano, Katsuhisa

    2015-10-01

    We investigated fatty acid oxidation by atmospheric-pressure nonthermal helium plasma using linoleic acid, an unsaturated fatty acid, together with evaluating active species induced in liquids. If the ambient gas contains oxygen, direct plasma such as plasma jets coming into contact with the liquid surface supplies various active species, such as singlet oxygen, ozone, and superoxide anion radicals, to the liquid. The direct plasma easily oxidizes linoleic acid, indicating that fatty acid oxidation will occur in the direct plasma. In contrast, afterglow flow, where the plasma is terminated in a glass tube and does not touch the surface of the liquid sample, supplies mainly superoxide anion radicals. The fact that there was no clear observation of linoleic acid oxidation using the afterglow reveals that it may not affect lipids, even in an atmosphere containing oxygen. The afterglow flow can potentially be used for the sterilization of aqueous solutions using the reduced pH method, in medical and dental applications, because it provides bactericidal activity in the aqueous solution despite containing a smaller amount of active species.

  16. 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

  17. 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.

  18. 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.

  19. Active rehabilitation in a pediatric extracorporeal membrane oxygenation patient.

    PubMed

    Zebuhr, Carleen; Sinha, Amit; Skillman, Heather; Buckvold, Shannon

    2014-05-01

    Decreased intensive care unit (ICU) mortality has led to an increase in ICU morbidity. ICU-induced immobilization plays a major role in this morbidity. Recently, ICU mobility has been shown to be safe and effective in adolescent and adult patients. We report the successful rehabilitation of an 8-year-old boy with severe acute respiratory distress syndrome on extracorporeal membrane oxygenation. A child who is critically ill may safely perform active rehabilitation while on venovenous extracorporeal membrane oxygenation. The gains achieved through active rehabilitation and optimal nutrition can facilitate recovery from severe acute respiratory distress syndrome in select pediatric patients on extracorporeal membrane oxygenation.

  20. Single Silver Adatoms on Nanostructured Manganese Oxide Surfaces: Boosting Oxygen Activation for Benzene Abatement.

    PubMed

    Chen, Yaxin; Huang, Zhiwei; Zhou, Meijuan; Ma, Zhen; Chen, Jianmin; Tang, Xingfu

    2017-02-21

    The involvement of a great amount of active oxygen species is a crucial requirement for catalytic oxidation of benzene, because complete mineralization of one benzene molecule needs 15 oxygen atoms. Here, we disperse single silver adatoms on nanostructured hollandite manganese oxide (HMO) surfaces by using a thermal diffusion method. The single-atom silver catalyst (Ag1/HMO) shows high catalytic activity in benzene oxidation, and 100% conversion is achieved at 220 °C at a high space velocity of 23 000 h(-1). The Mars-van Krevelen mechanism is valid in our case as the reaction orders for both benzene and O2 approach one, according to reaction kinetics data. Data from H2 temperature-programmed reduction and O core-level X-ray photoelectron spectra (XPS) reveal that Ag1/HMO possesses a great amount of active surface lattice oxygen available for benzene oxidation. Valence-band XPS and density functional theoretical calculations demonstrate that the single Ag adatoms have the upshifted 4d orbitals, thus facilitating the activation of gaseous oxygen. Therefore, the excellent activation abilities of Ag1/HMO toward both surface lattice oxygen and gaseous oxygen account for its high catalytic activity in benzene oxidation. This work may assist with the rational design of efficient metal-oxide catalysts for the abatement of volatile organic compounds such as benzene.

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

    PubMed

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

    2011-01-01

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

  2. 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.

  3. Sensitivity of dark mutants of various strains of luminescent bacteria to reactive oxygen species.

    PubMed

    Lyzeń, Robert; Wegrzyn, Grzegorz

    2005-03-01

    Recent studies indicated that bioluminescence of the marine bacterium Vibrio harveyi may both stimulate DNA repair and contribute to detoxification of deleterious oxygen derivatives. Therefore, it was also proposed that these reactions can be considered biological roles of bacterial luminescence and might act as evolutionary drives in development of luminous systems. However, experimental evidence for the physiological role of luciferase in protection of cells against oxidative stress has been demonstrated only in one bacterial species, raising the question whether this is a specific or a more general phenomenon. Here we demonstrate that in the presence of various oxidants (hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide and ferrous ions) growth of dark mutants of different strains of Vibrio fischeri and Photobacterium leiognathi is impaired relative to wild-type bacteria, though to various extents. Deleterious effects of oxidants on the mutants could be reduced (with different efficiency) by addition of antioxidants, A-TEMPO or 4OH-TEMPO. These results support the hypotheses that (1) activities of bacterial luciferases may detoxify deleterious oxygen derivatives, and (2) significantly different efficiencies of this reaction are characteristic for various luciferases.

  4. Silvering and swimming effects on aerobic metabolism and reactive oxygen species in the European eel.

    PubMed

    Amérand, Aline; Mortelette, Hélène; Belhomme, Marc; Moisan, Christine

    2017-01-01

    Silvering, the last metamorphosis in the eel life cycle induces morphological and physiological modifications in yellow eels (sedentary stage). It pre-adapts them to cope with the extreme conditions they will encounter during their 6000-km spawning migration. A previous study showed that silver eels are able to cope with reactive oxygen species (ROS) over-production linked to an increase in aerobic metabolism during sustained swimming, but the question remains as to whether this mechanism is associated with silvering. A sustained swimming session decreased red muscle in vitro mitochondrial oxygen consumption (MO2) but increased ROS production in both eel stages. The swimming exercise used here was perhaps too intense to induce a stimulation of mitochondrial function or biogenesis even when antioxidant enzyme activities were unchanged. Pro-oxidant/antioxidant imbalance by lipid peroxidation increased in yellow but significantly decreased in silver eels. The silvering process therefore appears to allow a pre-adaptation of red muscle radical metabolism to the demands of spawning migration.

  5. 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

  6. 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.

  7. The allelochemical L-DOPA increases melanin production and reduces reactive oxygen species in soybean roots.

    PubMed

    Soares, Anderson Ricardo; de Lourdes Lucio Ferrarese, Maria; de Cássia Siqueira-Soares, Rita; Marchiosi, Rogério; Finger-Teixeira, Aline; Ferrarese-Filho, Osvaldo

    2011-08-01

    The non-protein amino acid, L-3,4-dihydroxyphenylalanine (L-DOPA), is the main allelochemical released from the roots of velvetbean and affects seed germination and root growth of several plant species. In the work presented here, we evaluated, in soybean roots, the effects of L-DOPA on the following: polyphenol oxidase (PPO), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities; superoxide anion (O·-2), hydrogen peroxide (H(2)O(2)), and melanin contents; and lipid peroxidation. To this end, 3-day-old seedlings were cultivated in half-strength Hoagland's solution (pH 6.0), with or without 0.1 to 1.0 mM L-DOPA in a growth chamber (at 25°C, with a light/dark photoperiod of 12/12 hr and a photon flux density of 280 μmol m(-2) s(-1)) for 24 hr. The results showed that L-DOPA increased the PPO activity and, further, the melanin content. The activities of SOD and POD increased, but CAT activity decreased after the chemical exposure. The contents of reactive oxygen species (ROS), such as O·-2 and H(2)O(2), and the levels of lipid peroxidation significantly decreased under all concentrations of L-DOPA tested. These results suggest that L-DOPA was absorbed by the soybean roots and metabolized to melanin. It was concluded that the reduction in the O·-2 and H(2)O(2) contents and lipid peroxidation in soybean roots was due to the enhanced SOD and POD activities and thus a possible antioxidant role of L-DOPA.

  8. 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.

  9. 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.

  10. Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction

    PubMed Central

    Sun, Lingmei; Liao, Kai; Hang, Chengcheng; Wang, Dayong

    2017-01-01

    Objective To investigate the effects of honokiol on induction of reactive oxygen species (ROS), antioxidant defense systems, mitochondrial dysfunction, and apoptosis in Candida albicans. Methods To measure ROS accumulation, 2′,7′-dichlorofluorescein diacetate fluorescence was used. Lipid peroxidation was assessed using both fluorescence staining and a thiobarbituric acid reactive substances (TBARS) assay. Protein oxidation was determined using dinitrophenylhydrazine derivatization. Antioxidant enzymatic activities were measured using commercially available detection kits. Superoxide dismutase (SOD) genes expression was measured using real time RT-PCR. To assess its antifungal abilities and effectiveness on ROS accumulation, honokiol and the SOD inhibitor N,N′-diethyldithiocarbamate (DDC) were used simultaneously. Mitochondrial dysfunction was assessed by measuring the mitochondrial membrane potential (mtΔψ). Honokiol-induced apoptosis was assessed using an Annexin V-FITC apoptosis detection kit. Results ROS, lipid peroxidation, and protein oxidation occurred in a dose-dependent manner in C. albicans after honokiol treatment. Honokiol caused an increase in antioxidant enzymatic activity. In addition, honokiol treatment induced SOD genes expression in C. albicans cells. Moreover, addition of DDC resulted in increased endogenous ROS levels and potentiated the antifungal activity of honokiol. Mitochondrial dysfunction was confirmed by measured changes to mtΔψ. The level of apoptosis increased in a dose-dependent manner after honokiol treatment. Conclusions Collectively, these results indicate that honokiol acts as a pro-oxidant in C. albicans. Furthermore, the SOD inhibitor DDC can be used to potentiate the activity of honokiol against C. albicans. PMID:28192489

  11. Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation

    SciTech Connect

    Klein, Stefanie; Sommer, Anja; Distel, Luitpold V.R.; Neuhuber, Winfried; Kryschi, Carola

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Ultrasmall citrate-coated SPIONs with {gamma}Fe{sub 2}O{sub 3} and Fe{sub 3}O{sub 4} structure were prepared. Black-Right-Pointing-Pointer SPIONs uptaken by MCF-7 cells increase the ROS production for about 240%. Black-Right-Pointing-Pointer The SPION induced ROS production is due to released iron ions and catalytically active surfaces. Black-Right-Pointing-Pointer Released iron ions and SPION surfaces initiate the Fenton and Haber-Weiss reaction. Black-Right-Pointing-Pointer X-ray irradiation of internalized SPIONs leads to an increase of catalytically active surfaces. -- Abstract: Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces.

  12. 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.

  13. Texas Endangered Species Activity Book.

    ERIC Educational Resources Information Center

    Jackson, Kathleen Marie; Campbell, Linda

    This publication is the result of the Texas Parks and Wildlife Division's (TPWD's) commitment to education and the fertile partnerships formed between TPWD biologists and educators. This activity book brings together the expertise and practical knowledge of a classroom teacher with the technical knowledge and skills of a TPWD biologist and artist.…

  14. 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

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

    PubMed

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

    2012-02-01

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

  16. Interconnection of reactive oxygen species chemistry across the interfaces of atmospheric, environmental, and biological processes.

    PubMed

    Anglada, Josep M; Martins-Costa, Marilia; Francisco, Joseph S; Ruiz-López, Manuel F

    2015-03-17

    Oxidation reactions are ubiquitous and play key roles in the chemistry of the atmosphere, in water treatment processes, and in aerobic organisms. Ozone (O3), hydrogen peroxide (H2O2), hydrogen polyoxides (H2Ox, x > 2), associated hydroxyl and hydroperoxyl radicals (HOx = OH and HO2), and superoxide and ozonide anions (O2(-) and O3(-), respectively) are the primary oxidants in these systems. They are commonly classified as reactive oxygen species (ROS). Atmospheric chemistry is driven by a complex system of chain reactions of species, including nitrogen oxides, hydroxyl and hydroperoxide radicals, alkoxy and peroxy radicals, and ozone. HOx radicals contribute to keeping air clean, but in polluted areas, the ozone concentration increases and creates a negative impact on plants and animals. Indeed, ozone concentration is used to assess air quality worldwide. Clouds have a direct effect on the chemical composition of the atmosphere. On one hand, cloud droplets absorb many trace atmospheric gases, which can be scavenged by rain and fog. On the other hand, ionic species can form in this medium, which makes the chemistry of the atmosphere richer and more complex. Furthermore, recent studies have suggested that air-cloud interfaces might have a significant impact on the overall chemistry of the troposphere. Despite the large differences in molecular composition, concentration, and thermodynamic conditions among atmospheric, environmental, and biological systems, the underlying chemistry involving ROS has many similarities. In this Account, we examine ROS and discuss the chemical characteristics common to all of these systems. In water treatment, ROS are key components of an important subset of advanced oxidation processes. Ozonation, peroxone chemistry, and Fenton reactions play important roles in generating sufficient amounts of hydroxyl radicals to purify wastewater. Biochemical processes within living organisms also involve ROS. These species can come from pollutants in

  17. Activation of oxygen evolving perovskites for oxygen reduction by functionalization with Fe-N(x)/C groups.

    PubMed

    Rincón, Rosalba A; Masa, Justus; Mehrpour, Sara; Tietz, Frank; Schuhmann, Wolfgang

    2014-12-07

    The incorporation of Fe-Nx/C moieties into perovskites remarkably activates them for the oxygen reduction reaction (ORR) and also leads to notable improvement of their activity towards the oxygen evolution reaction (OER) thus presenting a new route for realizing high performance, low cost bifunctional catalysts for reversible oxygen electrodes.

  18. Transcription factors that defend bacteria against reactive oxygen species

    PubMed Central

    Imlay, James A.

    2015-01-01

    Bacteria live in a toxic world in which their competitors excrete hydrogen peroxide or superoxide-generating redox-cycling compounds. They protect themselves by activating regulons controlled by the OxyR, PerR, and SoxR transcription factors. OxyR and PerR sense peroxide when it oxidizes key thiolate or iron moieties, respectively; they then induce overlapping sets of proteins that defend their vulnerable metalloenzymes. An additional role for OxyR in detecting electrophilic compounds is possible. In some non-enteric bacteria SoxR appears to control the synthesis and export of redox-cycling compounds, whereas in the enteric bacteria it defends the cell against the same agents. When these compounds oxidize its iron-sulfur cluster, SoxR induces proteins that exclude, excrete, or modify them. It also induces enzymes that defend the cell against the superoxide that such compounds make. Recent work has brought new insight to the biochemistry and physiology of these responses, and comparative studies have clarified their evolutionary histories. PMID:26070785

  19. 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.

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

    PubMed

    Singh, Rachana; Parihar, Parul; Singh, Samiksha; Mishra, Rohit Kumar; Singh, Vijay Pratap; Prasad, Sheo Mohan

    2017-04-01

    Reactive oxygen species (ROS), a by-product of aerobic metabolism were initially studied in context to their damaging effect but recent decades witnessed significant advancements in understanding the role of ROS as signaling molecules. Contrary to earlier views, it is becoming evident that ROS production is not necessarily a symptom of cellular dysfunction but it might represent a necessary signal in adjusting the cellular machinery according to the altered conditions. Stomatal movement is controlled by multifaceted signaling network in response to endogenous and environmental signals. Furthermore, the stomatal aperture is regulated by a coordinated action of signaling proteins, ROS-generating enzymes, and downstream executors like transporters, ion pumps, plasma membrane channels, which control the turgor pressure of the guard cell. The earliest hallmarks of stomatal closure are ROS accumulation in the apoplast and chloroplasts and thereafter, there is a successive increase in cytoplasmic Ca(2+) level which rules the multiple kinases activity that in turn regulates the activity of ROS-generating enzymes and various ion channels. In addition, ROS also regulate the action of multiple proteins directly by oxidative post translational modifications to adjust guard cell signaling. Notwithstanding, an active progress has been made with ROS signaling mechanism but the regulatory action for ROS signaling processes in stomatal movement is still fragmentary. Therefore, keeping in view the above facts, in this mini review the basic concepts and role of ROS signaling in the stomatal movement have been presented comprehensively along with recent highlights.

  1. Phosphate enhances Fgf23 expression through reactive oxygen species in UMR-106 cells.

    PubMed

    Hori, Michiko; Kinoshita, Yuka; Taguchi, Manabu; Fukumoto, Seiji

    2016-03-01

    Fibroblast growth factor 23 (FGF23) has been shown to work as a phosphotropic hormone. Although FGF23 reduces the serum phosphate level, it has not been established that phosphate directly regulates FGF23 production. In this study, we investigated whether phosphate can enhance Fgf23 expression using the rat osteoblastic cell line UMR-106, which has been shown to express Fgf23 in response to 1,25-dihydroxyvitamin D [1,25(OH)2D]. Phosphate increased Fgf23 expression in a dose- and time-dependent manner in the presence of 1,25(OH)2D. Phosphate also increased Fgf23 promoter activity, but showed no effect on the half-life of Fgf23 messenger RNA. Phosphonoformic acid and PD98059, an inhibitor of MEK, inhibited the effects of phosphate on Fgf23 expression and promoter activity. In addition, phosphate enhanced production of reactive oxygen species (ROS) in UMR-106 cells, and hydrogen peroxide enhanced FGF23 production in a dose- and time-dependent manner. Hydrogen peroxide also enhanced Elk1 reporter activity, a target of the MEK-extracellular-signal-regulated kinase (ERK) pathway. Furthermore, the effect of phosphate on ROS production and Fgf23 expression was inhibited by apocynin, an inhibitor of NADPH oxidase. These results indicate that phosphate directly enhances Fgf23 transcription without affecting the stability of Fgf23 messenger RNA by stimulating NADPH-induced ROS production and the MEK-ERK pathway in UMR-106 cells.

  2. Decomposition of reactive oxygen species by copper(II) bis(1-pyrazolyl)methane complexes.

    PubMed

    Schepetkin, Igor; Potapov, Andrei; Khlebnikov, Andrei; Korotkova, Elena; Lukina, Anna; Malovichko, Galina; Kirpotina, Lilia; Quinn, Mark T

    2006-06-01

    Two bis(1-pyrazolyl)alkane ligands, bis(3,5-dimethyl-1-pyrazolyl)methane and bis(4-iodo-3,5-dimethyl-1-pyrazolyl)methane, and their copper(II) complexes, bis(3,5-dimethyl-1-pyrazolyl)methanedinitratocopper(II) [CuL1(NO3)2] and bis(4-iodo-3,5-dimethyl-1-pyrazolyl)methanedinitratocopper(II) [CuL2(NO3)2] x 2H2O, were prepared. Physiochemical properties of the copper(II) complexes were studied by spectroscopic (UV-vis, IR, EPR) techniques and cyclic voltammetry. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:copper(II) ion and a bidentate coordination mode for the nitrate ions in both of the complexes. According to experimental and theoretical ab initio data, the copper(II) ion is located in an octahedral hexacoordinated environment. Both complexes were able to catalyze the dismutation of superoxide anion (O2*-) (pH 7.5) and decomposition of H2O2 (pH 7.5) and peroxynitrite (pH 10.9). In addition, both complexes exhibited superoxide dismutase (SOD) like activity toward extracellular and intracellular reactive oxygen species produced by activated human neutrophils in whole blood. Thus, these complexes represent useful SOD mimetics with a broad range of antioxidant activity toward a variety of reactive oxidants.

  3. 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.

  4. Pseudomonas aeruginosa Pyocyanin Induces Neutrophil Death via Mitochondrial Reactive Oxygen Species and Mitochondrial Acid Sphingomyelinase

    PubMed Central

    Managò, Antonella; Becker, Katrin Anne; Carpinteiro, Alexander; Wilker, Barbara; Soddemann, Matthias; Seitz, Aaron P.; Edwards, Michael J.; Grassmé, Heike

    2015-01-01

    Abstract Aims: Pulmonary infections with Pseudomonas aeruginosa are a serious clinical problem and are often lethal. Because many strains of P. aeruginosa are resistant to antibiotics, therapeutic options are limited. Neutrophils play an important role in the host's early acute defense against pulmonary P. aeruginosa. Therefore, it is important to define the mechanisms by which P. aeruginosa interacts with host cells, particularly neutrophils. Results: Here, we report that pyocyanin, a membrane-permeable pigment and toxin released by P. aeruginosa, induces the death of wild-type neutrophils; its interaction with the mitochondrial respiratory chain results in the release of reactive oxygen species (ROS), the activation of mitochondrial acid sphingomyelinase, the formation of mitochondrial ceramide, and the release of cytochrome c from mitochondria. A genetic deficiency in acid sphingomyelinase prevents both the activation of this pathway and pyocyanin-induced neutrophil death. This reduced death, on the other hand, is associated with an increase in the release of interleukin-8 from pyocyanin-activated acid sphingomyelinase-deficient neutrophils but not from wild-type cells. Innovation: These studies identified the mechanisms by which pyocyanin induces the release of mitochondrial ROS and by which ROS induce neutrophil death via mitochondrial acid sphingomyelinase. Conclusion: These findings demonstrate a novel mechanism of pyocyanin-induced death of neutrophils and show how this apoptosis balances innate immune reactions. Antioxid. Redox Signal. 22, 1097–1110. PMID:25686490

  5. The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes.

    PubMed

    Cosentino, Marco; Luini, Alessandra; Bombelli, Raffaella; Corasaniti, Maria T; Bagetta, Giacinto; Marino, Franca

    2014-08-01

    Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration.

  6. Synergistic triggering of superoxide flashes by mitochondrial Ca2+ uniport and basal reactive oxygen species elevation.

    PubMed

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

    2013-02-15

    Mitochondrial superoxide flashes reflect a quantal, bursting mode of reactive oxygen species (ROS) production that arises from stochastic, transient opening of the mitochondrial permeability transition pore (mPTP) in many types of cells and in living animals. However, the regulatory mechanisms and the exact nature of the flash-coupled mPTP remain poorly understood. Here we demonstrate a profound synergistic effect between mitochondrial Ca(2+) uniport and elevated basal ROS production in triggering superoxide flashes in intact cells. Hyperosmotic stress potently augmented the flash activity while simultaneously elevating mitochondrial Ca(2+) and ROS. Blocking mitochondrial Ca(2+) transport by knockdown of MICU1 or MCU, newly identified components of the mitochondrial Ca(2+) uniporter, or scavenging mitochondrial basal ROS markedly diminished the flash response. More importantly, whereas elevating Ca(2+) or ROS production alone was inefficacious in triggering the flashes, concurrent physiological Ca(2+) and ROS elevation served as the most powerful flash activator, increasing the flash incidence by an order of magnitude. Functionally, superoxide flashes in response to hyperosmotic stress participated in the activation of JNK and p38. Thus, physiological levels of mitochondrial Ca(2+)