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Sample records for active oxygen species

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

    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.

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

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

    2016-02-01

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

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

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

  4. Chemically active species in an Oxygen Inductively Coupled Plasma

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

    2015-09-01

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

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

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

    1996-11-01

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

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

    Jennifer C. Molloy

    2015-08-01

    Full Text Available 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.

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

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

    2013-08-01

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

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

    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. PMID:21133411

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

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

    2011-01-01

    Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the pooriy differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyI-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, APOG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.

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

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

    2015-01-01

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

  11. Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production.

    Ye, Junli; Jiang, Zhongxin; Chen, Xuehong; Liu, Mengyang; Li, Jing; Liu, Na

    2016-01-15

    Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation. PMID:26511505

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

    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. 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. 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. 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

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

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

  14. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons

    Westlund Karin N

    2009-06-01

    Full Text Available Abstract Background Transient receptor potential vanilloid subtype 1 (TRPV1 is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1 activation. Reactive oxygen species (ROS production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and L5 DRGs were dissected bilaterally and cultured overnight. TRPV1 was stimulated with capsaicin or its potent analog, resiniferatoxin. ROS production was measured with live cell imaging and TNFR1 was detected with immunofluorescence in DRG primary cultures. The TRPV1 knockout mice, TRPV1 antagonist, capsazepine, and ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN, were employed to explore the functional relationship among TRPV1, ROS and TNFR1 in these studies. Results The results demonstrate that TRPV1 activation increases TNFR1 receptors and ROS generation in primary cultures of mouse DRG neurons. Activated increases in TNFR1 receptors and ROS production are absent in TRPV1 deficient mice. The PBN blocks increases in TNFR1 and ROS production induced by capsaicin/resiniferatoxin. Conclusion TRPV1 activation increases TNFR1 in cultured mouse DRG neurons through a ROS signaling pathway, a novel sensitization mechanism in DRG neurons.

  15. Reactive oxygen species are involved in regulating α1-adrenoceptor-activated vascular smooth muscle contraction

    Tsai Ming-Ho

    2010-08-01

    Full Text Available Abstract Background Reactive oxygen species (ROS were shown to mediate aberrant contractility in hypertension, yet the physiological roles of ROS in vascular smooth muscle contraction have remained elusive. This study aimed to examine whether ROS regulate α1-adrenoceptor-activated contraction by altering myosin phosphatase activities. Methods Using endothelium-denuded rat tail artery (RTA strips, effects of anti-oxidants on isometric force, ROS production, phosphorylation of the 20-kDa myosin light chain (MLC20, and myosin phosphatase stimulated by α1-adrenoceptor agonist phenylephrine were examined. Results An antioxidant, N-acetyl-L-cysteine (NAC, and two NADPH oxidase inhibitors, apocynin and VAS2870, dose-dependently inhibited contraction activated by phenylephrine. Phenylephrine stimulated superoxide anion production that was diminished by the pretreatment of apocynin, VAS2870, superoxide scavenger tiron or mitochondria inhibitor rotenone, but not by xanthine oxidase inhibitor allopurinol or cyclooxygenase inhibitor indomethacin. Concurrently, NADPH oxidase activity in RTA homogenates increased within 1 min upon phenylephrine stimulation, sustained for 10 min, and was abolished by the co-treatment with apocynin, but not allopurinol or rotenone. Phenylephrine-induced MLC20 phosphorylation was dose-dependently decreased by apocynin. Furthermore, apocynin inhibited phenylephrine-stimulated RhoA translocation to plasma membrane and phosphorylation of both myosin phosphatase regulatory subunit MYPT1Thr855 and myosin phosphatase inhibitor CPI-17Thr38. Conclusions ROS, probably derived from NADPH oxidase and mitochondria, partially regulate α1-adrenoceptor-activated smooth muscle contraction by altering myosin phosphatase-mediated MLC20 phosphorylation through both RhoA/Rho kinase- and CPI-17-dependent pathways.

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

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

    2014-05-01

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

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

    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

  18. Mechanistic and Synthetic Approaches for Activation of Water-and Oxygen-Species by Biomimetic Systems (Containing Manganese and Cobalt)

    Lieb, Dominik

    2013-01-01

    The current work deals with elementary reaction steps involved in the mechanisms that lead to the activation of water and oxygen species by biomimetic systems featuring redox-active manganese and cobalt centers, respectively. The first part of this work (Chapter 2 and Chapter 3) deals with the role of water exchange on metal centers that are relevant for water oxidation in nature. The first of two studies about this subject is addressing the role of manganese(III) in the oxygen evolving clust...

  19. Electrocatalytic Oxygen Evolution on Iridium Oxide: Uncovering Catalyst-Substrate Interactions and Active Iridium Oxide Species

    Reier, T.; Teschner, D; Lunkenbein, T.; Bergmann, A; Selve, S.; Kraehnert, R.; R. Schlögl; Strasser, P.

    2014-01-01

    The morphology, crystallinity, and chemical state of well-defined Ir oxide nanoscale thin-film catalysts prepared on Ti substrates at various calcination temperatures were investigated. Special emphasis was placed on the calcination temperature-dependent interaction between Ir oxide film and Ti substrate and its impact on the electrocatalytic oxygen evolution reaction (OER) activity. The Ir oxide films were characterized by scanning electron microscopy, transmission electron microscopy, scann...

  20. UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species

    Kooy, M. van M.; Akkerman, J.W.N.; Asbeck, S. van; Borghuis, Lizette; Prooijen, H.C. van (Utrecht Univ. Hospital (Netherlands))

    1993-02-01

    In the present study the authors have further investigated the routes of platelet activation following UVB exposure. Evidence is provided that UVB radiation does not activate the platelets via the classical Phospholipase A[sub 2] and Phospholipase C routes. Despite this observation, UVB-induced fibrinogen binding was found to be correlated with a 40% increase in phosphorylated 47 kD protein. Both findings could be completely inhibited in the presence of staurosporine, a potent inhibitor of protein kinase C (PK-C). In efforts to explain the mechanism of PK-C activation by UV radiation they found that both UV-induced PK-C activation and platelet aggregation were significantly reduced in the presence of specific scavengers for reactive oxygen species including superoxide dismutase and catalase. It is concluded that exposure of platelets to UVB radiation can activate PK-C via oxygen radicals, resulting in exposure of fibrinogen binding sites and subsequent platelet aggregation. (Author).

  1. Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

    Kazuma Higashisaka

    2014-01-01

    Full Text Available Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor-α (TNF-α compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ≤10 μm in diameter provoked a greater inflammatory response than soil dust samples containing particles >10 μm. In addition, Asian dust particles-induced TNF-α production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor-κB and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages.

  2. Active oxygen species and a degree of UV-modification of structural and functional properties of lactate dehydrogenase

    The spectrophotometry and photofluorescence techniques were used in the studies on photochemical transformations of lactate dehydrogenase exposed to UV-irradiation with a dose of 2.25 kJ/m2, in the native state and in the presence of exogenous modifiers: sodium azide, β-carotene, histidine, D-mannitol, and tret-butanol. It was shown that UV-irradiation of the mixtures of lactate dehydrogenase with sodium azide, β-carotene and histidine results in restoration (by 99, 65 and 63 %, respectively) of the level of catalytic activity of the enzyme as compared to that observed after irradiating in the absence of the protectors. The protective effect provided by mannitol during UV-irradiation of the lactate dehydrogenase was 23 %. Thus, it was shown that active oxygen species - singlet molecular oxygen and hydroxyl radical - make significant contributions to photomodification of lactate dehydrogenase. (author)

  3. Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

    Yoon TH

    2012-03-01

    Full Text Available Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2 has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70 together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein

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

    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.

  5. Mitochondrial reactive oxygen species enhance AMP-activated protein kinase activation in the endothelium of patients with coronary artery disease and diabetes

    Mackenzie, Ruth M.; Salt, Ian P.; Miller, William H.; et al.

    2013-01-01

    The aim of the present study was to determine whether the endothelial dysfunction associated with CAD (coronary artery disease) and T2D (Type 2 diabetes mellitus) is concomitant with elevated mtROS (mitochondrial reactive oxygen species) production in the endothelium and establish if this, in turn, regulates the activity of endothelial AMPK (AMP-activated protein kinase). We investigated endothelial function, mtROS production and AMPK activation in saphenous veins from patients with advanced ...

  6. Cadmium induces neuronal cell death through reactive oxygen species activated by GADD153

    Kim Seungwoo

    2013-01-01

    Full Text Available Abstract Background Cadmium(Cd, a heavy metal, which has a potent harmful effects, is a highly stress-inducible material that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER (so-called ER stress. The mechanism Cd induced cell death of neuroblastoma cells complex, involving cellular signaling pathways as yet incompletely defined but, in part, involving the generation of reactive oxygen species (ROS. Several studies have correlated GADD153 expression with cell death, but a mechanistic link between GADD153 and apoptosis has never been demonstrated. Results SH-SY5Y cells were treated Cd led to increase in intracellular ROS levels. ROS generation is not consistent with intracellular [Ca2+]. The exposure of neuroblastoma cells to Cd led to increase in intracellular GADD153 and Bak levels in a doses and time dependent manner. The induction of these genes by Cd was attenuated by NAC. Cd-induced apoptosis is decreased in GADD153 knockdown cells compared with normal cells. The effect of GADD153 on the binding of C/EBP to the Bak promoters were analyzed ChIP assay. Basal constitutive GADD153 recruitment to the –3,398/–3,380 region of the Bak promoter is observed in SH-SY5Y cells. Conclusions The exposure of SH-SY5Y cells to Cd led to increase in intracellular ROS levels in a doses and time dependent manner. The generation of ROS result in the induction of GADD153 is causative of cadmium-induced apoptosis. GADD153 regulates Bak expression by its binding to promoter region (between −3,398 and −3,380. Therefore, we conclude that GADD153 sensitizes cells to ROS through mechanisms that involve up-regulation of BAK and enhanced oxidant injury.

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

    Guthrie, H David; Welch, Glenn R

    2010-01-01

    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-diaza-s-indacene-3-undecanoic acid, C(11)BODIPY(581/591) (BODIPY). ROS was detected by red fluorescence emission from oxidization of HE and membrane lipid peroxidation was detected by green fluorescence emission from oxidation of BODIPY in individual live sperm. Of the reactive oxygen species generators tested, BODIPY oxidation was specific for FeSo4/ascorbate (FeAc), because menadione and H(2)O(2) had little or no effect. The oxidization of hydroethidine to ethidium was specific for menadione and H(2)O(2); FeAc had no effect. The incidence of basal or spontaneous ROS formation and membrane lipid peroxidation were low in boar sperm (semen or after low temperature storage; however the sperm were quite susceptible to treatment-induced ROS formation and membrane lipid peroxidation. PMID:20072917

  8. Can systemically generated reactive oxygen species help to monitor disease activity in generalized vitiligo? A pilot study

    Richeek Pradhan

    2014-01-01

    Full Text Available Background: Generalized vitiligo is a disease with unpredictable bursts of activity, goal of treatment during the active phase being to stabilize the lesions. This emphasizes the need for a prospective marker for monitoring disease activity to help decide the duration of therapy. Aims and Objectives: In the present study, we examined whether reactive oxygen species (ROS generated in erythrocytes can be translated into a marker of activity in vitiligo. Materials and Methods: Level of intracellular ROS was measured flow cytometrically in erythrocytes from venous blood of 21 patients with generalized vitiligo and 21 healthy volunteers using the probe dichlorodihydrofluorescein diacetate. Results: The levels of ROS differed significantly between patients and healthy controls, as well as between active versus stable disease groups. In the active disease group, ROS levels were significantly lower in those being treated with systemic steroids than those that were not. ROS levels poorly correlated with disease duration or body surface area involved. Conclusion: A long-term study based on these findings can be conducted to further validate the potential role of ROS in monitoring disease activity vitiligo.

  9. Uncoupled O2-activation in the human HIF-asparaginyl hydroxylase, FIH, does not produce reactive oxygen species

    Saban, Evren; Flagg, Shannon C.; Knapp, Michael J.

    2011-01-01

    The factor inhibiting HIF (FIH) is one of the primary oxygen sensors in human cells, controlling gene expression by hydroxylating the α-subunit of the hypoxia inducible transcription factor (HIF). As FIH is an alpha-ketoglutarate dependent non-heme iron dioxygenase, oxygen activation is thought to precede substrate hydroxylation. The coupling between oxygen activation and substrate hydroxylation was hypothesized to be very tight, in order for FIH to fulfill its function as a regulatory enzyme...

  10. Effects of nitrogen dioxide and its acid mist on reactive oxygen species production and antioxidant enzyme activity in Arabidopsis plants.

    Liu, Xiaofang; Hou, Fen; Li, Guangke; Sang, Nan

    2015-08-01

    Nitrogen dioxide (NO2) is one of the most common and harmful air pollutants. To analyze the response of plants to NO2 stress, we investigated the morphological change, reactive oxygen species (ROS) production and antioxidant enzyme activity in Arabidopsis thaliana (Col-0) exposed to 1.7, 4, 8.5, and 18.8 mg/m(3) NO2. The results indicate that NO2 exposure affected plant growth and chlorophyll (Chl) content, and increased oxygen free radical (O2(-)) production rate in Arabidopsis shoots. Furthermore, NO2 elevated the levels of lipid peroxidation and protein oxidation, accompanied by the induction of antioxidant enzyme activities and change of ascorbate (AsA) and glutathione (GSH) contents. Following this, we mimicked nitric acid mist under experimental conditions, and confirmed the antioxidant mechanism of the plant to the stress. Our results imply that NO2 and its acid mist caused pollution risk to plant systems. During the process, increased ROS acted as a signal to induce a defense response, and antioxidant status played an important role in plant protection against NO2/nitric acid mist-caused oxidative damage. PMID:26257351

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

    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

  12. Cytotoxicity of, and DNA damage by, active oxygen species produced by xanthine oxidase.

    Chiricolo, M; Tazzari, P L; Abbondanza, A; Dinota, A; Battelli, M G

    1991-10-21

    Toxicity to Raji cells of the xanthine oxidase/hypoxanthine system is related to the formation of single-strand DNA breaks. DNA damage was proportional to the concentration of xanthine oxidase and to the time of exposure. It was prevented by the absence of hypoxanthine, or by the presence of allopurinol, or both superoxide dismutase and catalase. The release of 51Cr from damaged cells was detectable 12 h after the inhibition of cloning efficiency and the production of DNA breakage. These data suggest that DNA damage induced by the oxygen products precedes the severe lesion to the cellular membrane. PMID:1936259

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

    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 μg/ml) and the analysis was performed after 0.5, 2, 6, and 24 h exposure. All wood dusts studied were cytotoxic to human bronchial epithelial cells in a dose-dependent manner after 2 and 6 h 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 6 h 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 NFκB or AP-1 may play a role in this wood dust-evoked process leading to apparently induced apoptosis of target cells.

  14. Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

    Huang, Ying-Ying; Tomkinson, Elizabeth M.; Sharma, Sulbha K.; Kharkwal, Gitika B.; Saleem, Taimur; Mooney, David; Yull, Fiona E.; Blackwell, Timothy S.; Hamblin, Michael R.

    2011-01-01

    Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings 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 NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT. PMID:21814580

  15. Influence of reactive oxygen species on the enzyme stability and activity in the presence of ionic liquids.

    Pankaj Attri

    Full Text Available 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.

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

    Aaron C-H Chen

    Full Text Available BACKGROUND: Despite over forty years of investigation on low-level light therapy (LLLT, the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: 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 NF-kB was observed at fluences higher than 0.003 J/cm(2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. CONCLUSION: We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.

  17. Promoting Active Species Generation by Plasmon-Induced Hot-Electron Excitation for Efficient Electrocatalytic Oxygen Evolution.

    Liu, Guigao; Li, Peng; Zhao, Guixia; Wang, Xin; Kong, Jintao; Liu, Huimin; Zhang, Huabin; Chang, Kun; Meng, Xianguang; Kako, Tetsuya; Ye, Jinhua

    2016-07-27

    Water splitting represents a promising technology for renewable energy conversion and storage, but it is greatly hindered by the kinetically sluggish oxygen evolution reaction (OER). Here, using Au-nanoparticle-decorated Ni(OH)2 nanosheets [Ni(OH)2-Au] as catalysts, we demonstrate that the photon-induced surface plasmon resonance (SPR) excitation on Au nanoparticles could significantly activate the OER catalysis, specifically achieving a more than 4-fold enhanced activity and meanwhile affording a markedly decreased overpotential of 270 mV at the current density of 10 mA cm(-2) and a small Tafel slope of 35 mV dec(-1) (no iR-correction), which is much better than those of the benchmark IrO2 and RuO2, as well as most Ni-based OER catalysts reported to date. The synergy of the enhanced generation of Ni(III/IV) active species and the improved charge transfer, both induced by hot-electron excitation on Au nanoparticles, is proposed to account for such a markedly increased activity. The SPR-enhanced OER catalysis could also be observed over cobalt oxide (CoO)-Au and iron oxy-hydroxide (FeOOH)-Au catalysts, suggesting the generality of this strategy. These findings highlight the possibility of activating OER catalysis by plasmonic excitation and could open new avenues toward the design of more-energy-efficient catalytic water oxidation systems with the assistance of light energy. PMID:27380539

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

    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.

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

    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.

  20. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury.

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-04-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo-induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3(-/-)) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  1. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-01-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo–induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3−/−) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  2. Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation.

    Liu, Ju Mei; Pan, Feng; Li, Li; Liu, Qian Rong; Chen, Yong; Xiong, Xin Xin; Cheng, Kejun; Yu, Shang Bin; Shi, Zhi; Yu, Albert Cheung-Hoi; Chen, Xiao Qian

    2013-07-19

    Piperlongumine (PL), a natural alkaloid isolated from the long pepper, may have anti-cancer properties. It selectively targets and kills cancer cells but leaves normal cells intact. Here, we reported that PL selectively killed glioblastoma multiforme (GBM) cells via accumulating reactive oxygen species (ROS) to activate JNK and p38. PL at 20μM could induce severe cell death in three GBM cell lines (LN229, U87 and 8MG) but not astrocytes in cultures. PL elevated ROS prominently and reduced glutathione levels in LN229 and U87 cells. Antioxidant N-acetyl-L-cysteine (NAC) completely reversed PL-induced ROS accumulation and prevented cell death in LN229 and U87 cells. In LN229 and U87 cells, PL-treatment activated JNK and p38 but not Erk and Akt, in a dosage-dependent manner. These activations could be blocked by NAC pre-treatment. JNK and p38 specific inhibitors, SB203580 and SP600125 respectively, significantly blocked the cytotoxic effects of PL in LN229 and U87 cells. Our data first suggests that PL may have therapeutic potential for one of the most malignant and refractory tumors GBM. PMID:23796709

  3. The antimicrobial activity of prototype modified honeys that generate reactive oxygen species (ROS) hydrogen peroxide

    Cooke, Jonathan; Dryden, Matthew; Patton, Thomas; Brennan, James; Barrett, John

    2015-01-01

    Background Antimicrobial resistance continues to be a global issue in healthcare organisations. Honey has long been shown to possess wound healing and antimicrobial properties that are dependent on a number of physical and chemical properties of the honey. We tested the antimicrobial activity of a medicinal honey, Surgihoney® (SH) and two prototype modified honeys made by Apis mellifera (honeybee) against Staphylococcus aureus (NCIMB 9518). We also examined the modified honey prototypes for t...

  4. Reactive Oxygen Species Scavenging Activity of Flavone Glycosides from Melilotus neapolitana

    Pietro Monaco

    2007-02-01

    Full Text Available One new and six known flavone glycosides were isolated from the MeOH extract of Melilotus neapolitana Ten. The new compound, identified as 7-O-β-D-gluco-pyranosyloxy-4',5-dihydroxy-3-[O-α-L-rhamnopyranosyl-(1→6-3-O-β-D-glucopyrano-syloxy]flavone (1 by 1D and 2D NMR techniques and mass spectra, was isolated along with kaempferol-3-O-rutinoside (2, kaempferol-3-O-glucoside (3, rutin (4, quercetin-3-O-glucoside (5, isorhamnetin-3-O-rutinoside (6, and isorhamnetin-3-O-glucoside (7. The antioxidant and radical scavenging activities of these compounds and the whole crude methanol extract were evaluated. The organic extract can inhibit MDA marker’s synthesis by 57%. All the metabolites displayed good reducing power, with the kaempferol (2,3 and isorhamnetin derivatives (6,7 being less active than the corresponding quercetin derivatives 4,5.

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

    Lin, Chu-Cheng; Lin, Chuan-En; Lin, Yueh-Chien [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Ju, Tsai-Kai [Instrumentation Center, National Taiwan University, Taipei, Taiwan, ROC (China); Technology Commons, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Huang, Yuan-Li [Department of Biotechnology, Asia University, Taichung, Taiwan, ROC (China); Lee, Ming-Shyue [Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC (China); Chen, Jiun-Hong [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Lee, Hsinyu, E-mail: hsinyu@ntu.edu.tw [Institute of Zoology, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC (China); Center for Biotechnology, National Taiwan University, Taipei, Taiwan, ROC (China); Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan, ROC (China)

    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.

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

    Highlights: •LPA induces ROS generation through LPA1 and LPA3. •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 LPA1 and LPA3 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

  7. Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells

    YUAN Yan; BIAN Jian Chun; LIU Zong Ping; WANG Yi; HU Fei Fei; JIANG Chen Yang; ZHANG Ya Jing; YANG Jin Long; ZHAO Shi Wen; GU Jian Hong; LIU Xue Zhong

    2016-01-01

    ObjectiveTo examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells. MethodsNeuronal cells (primary rat cerebral cortical neurons and PC12cells) were incubated with or without Cd post-pretreatment with rapamycin (Rap) or N-acetyl-L-cysteine (NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3'-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. ResultsCd-induced activation of Akt/mTOR signaling, including Akt, mTOR,p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1(4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein (Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor(AIF)and endonuclease G (Endo G). ConclusionCd-induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis ofneuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases.

  8. Emodin-Induced Generation of Reactive Oxygen Species Inhibits RhoA Activation to Sensitize Gastric Carcinoma Cells to Anoikis

    Jun Cai

    2008-01-01

    Full Text Available RhoA is a critical signaling molecule regulating a variety of cellular processes, such as cytoskeletal organization, adhesion, and apoptosis. It is recently considered responsive to reactive oxygen species (ROS. Nevertheless, how RhoA regulates anoikis, a detachment-initiated apoptosis, and how this regulation is affected by ROS are not clear. The present study investigated the role of RhoA in apoptosis/anoikis in gastric cancer cells and the changes of RhoA and anoikis under oxidative stress. Immunohistochemistry showed that RhoA expression was upregulated in the primary gastric carcinoma compared with normal gastric mucosa. Overactivation of RhoA by transfection with the V14RhoA mutant prevented gastric cancer line SGC-7901 cells from arsenic-induced apoptosis and conferred anoikis resistance through, at least in part, promoting formations of F-actin fibers and focal adhesion. Oxidative stress caused by emodin, an ROS producer, in combination with arsenic trioxide (ATO led to RhoA inactivation that triggered structural disruption of focal adhesion complex and eventually resulted in anoikis, and these effects could be partially reversed by antioxidant N-acetylcysteine (NAC. In conclusion, activation of RhoA is required for the maintenance of anoikis resistance phenotype of gastric cancer cells, and oxidative stress might be a therapeutic strategy for the inhibition of RhoA in cancer cells.

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

    Ling Zhao

    2015-01-01

    Full Text Available 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.

  10. Canine parvovirus NS1 induced apoptosis involves mitochondria, accumulation of reactive oxygen species and activation of caspases.

    Gupta, Shishir Kumar; Sahoo, Aditya Prasad; Rosh, Nighil; Gandham, Ravi Kumar; Saxena, Lovleen; Singh, Arvind Kumar; Harish, D R; Tiwari, Ashok Kumar

    2016-02-01

    The non-structural protein (NS1) of parvoviruses plays an important role in viral replication and is thought to be responsible for inducing cell death. However, the detailed mechanism and the pathways involved in canine parvovirus type 2 NS1 (CPV2.NS1) induced apoptosis are not yet known. In the present study, we report that expression of CPV2.NS1 in HeLa cells arrests cells in G1 phase of the cell cycle and the apoptosis is mitochondria mediated as indicated by mitochondrial depolarization, release of cytochrome-c and activation of caspase 9. Treatment of cells with caspase 9 inhibitor Z-LEHD-FMK reduced the induction of apoptosis significantly. We also report that expression of CPV2.NS1 causes accumulation of reactive oxygen species (ROS) and treatment with an antioxidant reduces the ROS levels and the extent of apoptosis. Our results provide an insight into the mechanism of CPV2.NS1 induced apoptosis, which might prove valuable in developing NS1 protein as an oncolytic agent. PMID:26555166

  11. Distinct Mechanisms of Receptor and Nonreceptor Tyrosine Kinase Activation by Reactive Oxygen Species in Vascular Smooth Muscle Cells: Role of Metalloprotease and Protein Kinase C-δ

    Frank, Gerald D.; Mifune, Mizuo; Inagami, Tadashi; Ohba, Motoi; Sasaki, Terukatsu; Higashiyama, Shigeki; Dempsey, Peter J; Eguchi, Satoru

    2003-01-01

    Reactive oxygen species (ROS) are implicated in cardiovascular diseases. ROS, such as H2O2, act as second messengers to activate diverse signaling pathways. Although H2O2 activates several tyrosine kinases, including the epidermal growth factor (EGF) receptor, JAK2, and PYK2, in vascular smooth muscle cells (VSMCs), the intracellular mechanism by which ROS activate these tyrosine kinases remains unclear. Here, we identified two distinct signaling pathways required for receptor and nonreceptor...

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

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

    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 (C...

  13. ENDOTHELIN ACTIVATION OF REACTIVE OXYGEN SPECIES MEDIATES STRESS-INDUCED PRESSOR RESPONSE IN DAHL-SALT SENSITIVE PREHYPERTENSIVE RATS

    D’Angelo, Gerard; Loria, Analia S.; Pollock, David M.; Pollock, Jennifer S.

    2010-01-01

    Experiments were designed to test the hypothesis that endothelin and/or reactive oxygen species contribute to the pressor response induced by acute air jet stress in normotensive Dahl salt-sensitive rats maintained on a normal salt diet (pre-hypertensive). Mean arterial pressure was chronically monitored by telemetry before and after 3-day treatment with the free radical scavenger, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol), or endothelin receptor antagonists, ABT-627 (ETA antagonis...

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

    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 1α (HIF-1α), 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 (H2O2)-induced dysregulation of adiponectin and PAI-1 production. H2O2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), but had no effect on HIF-1α, whereas hypoxia stabilized HIF-1α and decreased expression of C/EBPα, but not PPARγ. 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

  15. Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation

    Bruder-Nascimento, T; Chinnasamy, P; Riascos-Bernal, DF; Cau, SB; Callera, GE; Touyz, RM; Tostes, RC; Sibinga, NES

    2014-01-01

    Fat1 is an atypical cadherin that controls vascular smooth muscle cell (VSMC) proliferation and migration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) is an important source of reactive oxygen species (ROS) in VSMCs. Angiotensin II (Ang II) induces the expression and/or activation of both Fat1 and Nox1 proteins. This study tested the hypothesis that Ang II-induced Fat1 activation and VSMC migration are mediated by Nox1-dependent ROS generation and redox signaling. Stu...

  16. Competition of CO and H2 for Active Oxygen Species during the Preferential CO Oxidation (PROX on Au/TiO2 Catalysts

    Yeusy Hartadi

    2016-01-01

    Full Text Available Aiming at an improved mechanistic understanding of the preferential oxidation of CO on supported Au catalysts, we have investigated the competition between CO and H2 for stable, active oxygen (Oact species on a Au/TiO2 catalyst during the simultaneous exposure to CO and H2 with various CO/H2 ratios at 80 °C and 400 °C by quantitative temporal analysis of products (TAP reactor measurements. It is demonstrated that, at both higher and lower temperature, the maximum amount of active oxygen removal is (i independent of the CO/H2 ratio and (ii identical to the amount of active oxygen removal by CO or H2 alone. Hence, under preferential CO oxidation (PROX reaction conditions, in the simultaneous presence of CO and H2, CO and H2 compete for the same active oxygen species. In addition, also the dependency of the selectivity towards CO oxidation on the CO/H2 ratio was evaluated from these measurements. Consequences of these findings on the mechanistic understanding of the PROX reaction on Au/TiO2 will be discussed.

  17. Structure of Dihydrochalcones and Related Derivatives and Their Scavenging and Antioxidant Activity against Oxygen and Nitrogen Radical Species

    Alexandre L. A. Bentes

    2011-02-01

    Full Text Available 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 (DEiso 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.

  18. The Scavenging of Free Radical and Oxygen Species Activities and Hydration Capacity of Collagen Hydrolysates from Walleye Pollock (Theragra chalcogramma) Skin

    ZHUANG Yongliang; LI Bafang; ZHAO Xue

    2009-01-01

    Fish skin collagen hydrolysates (FSCH) were prepared from walleye pollock (Theragra chalcogramma) using a mixture of enzymes, namely trypsin and flavourzyme. The degree of hydrolysis of the skin collagen was 27.3%. FSCH was mainly composed of low-molecular-weight peptides and the relative proportion of <1000Da fraction was 70.6%. Free radical and oxygen species scavenging activities of FSCH were investigated in four model systems, including diphenylpicrylhy-drazyl radical (DPPH), superox-ide anion radical, hydroxyl radical and hydrogen peroxide model, and compared with that of a native antioxidant, reduced glutathione (GSH). FSCH was also evaluated by water-absorbing and water-holding capacity. The results showed that FSCH was able to scav-enge free radical and oxygen species significantly and to enhance water-absorbing and water-holding capacity remarkably. Therefore, FSCH may have potential applications in the medicine and food industries.

  19. Induction of benzo[a]pyrene Mono-oxygenase in liver cell culture by the photochemical generation of active oxygen species. Evidence for the involvement of singlet oxygen and the formation of a stable inducing intermediate.

    Paine, A J

    1976-07-15

    1. The photochemical generation of excited states of oxygen in liver cell culture by the mild ilumination of culture medium containing riboflavin, results in stimulation of benzo[a]pyrene 3-mono-oxygenase, a cytochrome P-450-linked mono-oxygenase. 2. The same large increase in mono-oxygenase activity was found when medium containing riboflavin was illuminated in the absence of cells and then stored in the dark for 24h before contact with the cells. From this it may be inferred that stimulation is due to the formation of a stable inducer in the culture medium. Further experiments indicate that the stable inducer is due to the photo-oxidation of an amino acid. 3. Evidence that singlet oxygen is responsible for initiating the stimulation of the mono-oxygenase is based on the use of molecules that scavenge particular active oxygen species. Of all the scavengers tested, only those that scavenge single oxygen inhibited the stimulation. 4. A hypothesis is developed to relate the stimulation of the mono-oxygenase by singlet oxygen in cultured cells to the regulation of the cytochrome P-450 enzyme system in vivo. It is suggested that single oxygen generation within cells may be a common factor linking the many structurally diverse inducers of the enzyme system. PMID:962887

  20. Rosacea, Reactive Oxygen Species, and Azelaic Acid

    Jones, David A.

    2009-01-01

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

  1. Diphenyleneiodonium inhibits NF-kappaB activation and iNOS expression induced by IL-1beta: involvement of reactive oxygen species

    Mendes, A. Ferreira; Carvalho, A. Pato; Caramona, M. Margarida; Lopes, M. Celeste

    2001-01-01

    AIMS: In this work, we studied the mechanisms by which diphenyleneiodonium chloride (DPI) inhibits nitric oxide (NO) synthesis induced by the proinflammatory cytokine interleukin-1beta (IL-1) in bovine articular chondrocytes. To achieve this, we evaluated the ability of DPI to inhibit the expression and activity of the inducible isoform of the NO synthase (iNOS) induced by IL-1. We also studied the ability of DPI to prevent IL-1-induced NF-kappaB activation and reactive oxygen species (ROS) p...

  2. Diphenyleneiodonium inhibits NF-κB activation and iNOS expression induced by IL-1β: involvement of reactive oxygen species

    A. Ferreira Mendes; A. Pato Carvalho; M. Margarida Caramona; M. Celeste Lopes

    2001-01-01

    Aims: In this work, we studied the mechanisms by which diphenyleneiodonium chloride (DPI) inhibits nitric oxide (NO) synthesis induced by the pro-inflammatory cytokine interleukin-1β (IL-1) in bovine articular chondrocytes. To achieve this, we evaluated the ability of DPI to inhibit the expression and activity of the inducible isoform of the NO synthase (iNOS) induced by IL-1. We also studied the ability of DPI to prevent IL-1-induced NF-κB activation and reactive oxygen species (ROS) product...

  3. Wear Particles Impair Antimicrobial Activity Via Suppression of Reactive Oxygen Species Generation and ERK1/2 Phosphorylation in Activated Macrophages.

    Chen, Weishen; Li, Ziqing; Guo, Ying; Zhou, Yuhuan; Zhang, Yangchun; Luo, Guotian; Yang, Xing; Li, Chaohong; Liao, Weiming; Sheng, Puyi

    2015-01-01

    Implant-related infection (IRI) is closely related to the local immunity of peri-implant tissues. The generation of reactive oxygen species (ROS) in activated macrophages plays a prominent role in the innate immune response. In previous studies, we indicated that implant wear particles promote endotoxin tolerance by decreasing the release of proinflammatory cytokines. However, it is unclear whether ROS are involved in the damage of the local immunity of peri-implant tissues. In the present study, we assessed the mechanism of local immunosuppression using titanium (Ti) particles and/or lipopolysaccharide (LPS) to stimulate RAW 264.7 cells. The results indicate that the Ti particles induced the generation of a moderate amount of ROS through nicotinamide adenine dinucleotide phosphate oxidase-1, but not through catalase. Pre-exposure to Ti particles inhibited ROS generation and extracellular-regulated protein kinase activation in LPS-stimulated macrophages. These findings indicate that chronic stimulation by Ti particles may lead to a state of oxidative stress and persistent inflammation, which may result in the attenuation of the immune response of macrophages to bacterial components such as LPS. Eventually, immunosuppression develops in peri-implant tissues, which may be a risk factor for IRI. PMID:25577344

  4. 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

    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 (H2O2) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H2O2 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 treated with nicotine

  5. 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

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do, E-mail: ydjung@chonnam.ac.kr

    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

  6. Synergistic effect of single-electron-trapped oxygen vacancies and carbon species on the visible light photocatalytic activity of carbon-modified TiO2

    Carbon-modified TiO2 (CT) nanoparticles were prepared via a two-step method of heat treatment without the resorcinol-formaldehyde (RF) polymer. As-prepared CT nanoparticles were characterized by means of X-ray diffraction (XRD), UV–Vis diffuse reflectance spectroscopy (UV–Vis/DRS), transmission electron microscopy (TEM), N2 adsorption–desorption isotherms, thermal analysis (TA), electron spin resonance (ESR), and X-ray photoelectron spectroscopy (XPS). The visible light photocatalytic activities were evaluated on the basis of the degradation of methyl orange (MO). The synergistic effect of single-electron-trapped oxygen vacancies (SETOVs) and the carbon species on the visible light photocatalytic activities of the CT nanoparticles were discussed. It was found that the crystalline phase, the morphology, and particle size of the CT nanoparticles depended on the second heat-treatment temperature instead of the first heat-treatment temperature. The visible light photocatalytic activities were attributed to the synergistic effect of SETOVs and the carbon species, and also depended on the specific surface area of the photocatalysts. - Highlights: • Carbon-modified TiO2 particles have been prepared without RF polymer. • The visible light photocatalytic activities of the particles have been evaluated. • The band gap energy structure of the carbon-modified TiO2 has been proposed. • Synergistic effect of SETOVs and carbon species has been discussed. • The activities also depend on the specific surface area of the catalysts

  7. Physical exercise, reactive oxygen species and neuroprotection.

    Radak, Zsolt; Suzuki, Katsuhiko; Higuchi, Mitsuru; Balogh, Laszlo; Boldogh, Istvan; Koltai, Erika

    2016-09-01

    Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS-mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation. PMID:26828019

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

    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

    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...

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

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

    2016-03-01

    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. PMID:26883897

  10. Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation

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

    2012-01-01

    Although the exact mechanism through which NADPH oxidases (Nox’s) generate reactive oxygen species (ROS) is still not completely understood, it is widely considered that ROS accumulation is the cause of oxidative stress in endothelial cells. Increasing pieces of evidence strongly indicate the role for ROS in endothelial inflammation and dysfunction and subsequent development of atherosclerotic plaques, which are causes of various pathological cardiac events. An overview for a causative relati...

  11. Reactive oxygen species and redox compartmentalization

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

    2014-01-01

    Reactive oxygen species (ROS) formation and signaling are of major importance and regulate a number of processes in physiological conditions. A disruption in redox status regulation, however, has been associated with numerous pathological conditions. In recent years it has become increasingly clear that oxidative and reductive modifications are confined in a spatio-temporal manner. This makes ROS signaling similar to that of Ca2+ or other second messengers. Some subcellular compartments are m...

  12. Mercury-induced apoptosis and necrosis in murine macrophages: role of calcium-induced reactive oxygen species and p38 mitogen-activated protein kinase signaling

    The current study characterizes the mechanism by which mercury, a toxic metal, induces death in murine macrophages. The cytotoxic EC50 of mercury ranged from 62.7 to 81.1 μM by various assays in J774A.1 cultures; accordingly, we employed 70 μM of mercuric chloride in most experiments. Mercury-induced intracellular calcium modulated reactive oxygen species (ROS) production, which resulted in both cell apoptosis and necrosis indicated by annexin V binding and caspase-3 activity, and propidium-iodide binding. Calcium antagonists abolished ROS production. Mercury stimulated p38 mitogen-activated protein kinase (MAPK) and additively stimulated lipopolysaccharide-activated p38. Mercury-activated p38 was decreased by pretreatment of cells with antioxidants, N-acetylcysteine (NAC) and silymarin, indicating that mercury-induced ROS were involved in p38 activation. Mercury increased the expression of tumor necrosis factor α (TNFα); antioxidants and a specific p38 inhibitor decreased this effect. Pretreatment with antioxidants, p38 inhibitor, and anti-TNFα antibody decreased mercury-induced necrosis; however, anti-TNFα antibody did not decrease mercury-induced apoptosis. Results suggest that mercury-induced macrophage death is a mix of apoptosis and necrosis employing different pathways. P38-mediated caspase activation regulates mercury-induced apoptosis and p38-mediated TNFα regulates necrosis in these cells. Calcium regulates ROS production and mercury-induced ROS modulate downstream p38 that regulates both apoptosis and necrosis

  13. Fractionating ambient humic-like substances (HULIS) for their reactive oxygen species activity - Assessing the importance of quinones and atmospheric aging

    Verma, Vishal; Wang, Ying; El-Afifi, Rawan; Fang, Ting; Rowland, Janessa; Russell, Armistead G.; Weber, Rodney J.

    2015-11-01

    In this paper, we present a technique to identify the redox-active components of fine organic aerosols by fractionating humic-like substances (HULIS). We applied this technique to a dithiothreitol (DTT) assay - a measure of the capability of PM to generate reactive oxygen species (ROS), and assessed the contribution of quinones to the DTT activity of ambient water-soluble PM. Filter samples from the Southeastern Center for Air Pollution & Epidemiology (SCAPE) were extracted in water and then passed-through a C-18 column to isolate the HULIS fraction by retention on the column. The HULIS was then eluted with a sequence of solvents of increasing polarity, i.e., hexane, dichloromethane (DCM) and then methanol. Each of these eluted fractions was analyzed for DTT activity. The methanol fraction was found to possess most of the DTT activity (>70%), while the hexane fraction had the least activity (60%) eluted in methanol. The results demonstrate the importance of atmospheric aging (oxidation) of organic aerosols in enhancing the ROS activity of ambient PM.

  14. Platycodin D induces reactive oxygen species-mediated apoptosis signal-regulating kinase 1 activation and endoplasmic reticulum stress response in human breast cancer cells.

    Yu, Ji Sun; Kim, An Keun

    2012-08-01

    Platycodin D (PD), a natural compound found in Platycodon grandiflorum, induces apoptotic cell death in various carcinoma cells. One mechanism of PD-mediated cell death is by activation of mitogen-activated protein kinases, as suggested in a recent report. In this study, we further examined upstream signal pathways and the relationship between these signals and reactive oxygen species (ROS). Using immunoblotting assays, we found that PD activated apoptosis signal-regulating kinase 1 (ASK1) through phosphorylation of ASK1 at threonine and dephosphorylation of ASK1 at serine. We also showed that PD caused activation of the endoplasmic reticulum (ER) stress response. This was supported by observations showing that treatment with PD induces phosphorylation of PKR-like ER kinase (PERK) and eukaryotic initiation factor 2 α (eIF 2α), up-regulating expression of glucose-regulated protein 78/immunoglobulin heavy chain binding protein (GRP78/Bip) and CCAAT/enhancer-binding protein homologous protein/growth arrest and DNA damage-inducible gene 153 (CHOP/GADD153) and activation of caspase-4. Furthermore, PD-induced ASK1 and ER stress responses were inhibited by the antioxidant N-acetyl-l-cysteine. These results suggest that ROS play a critical role for activation of ASK1 and ER stress in PD-treated cancer cells. PMID:22784044

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

    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 {t...

  16. Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

    Fanxiang Zeng; Li Tian; Fei Liu; Jianguo Cao; Meifang Quan; Xifeng Sheng

    2012-01-01

    Casticin,a polymethoxyflavone from Fructus viticis used as an anti-inflammatory agent in Chinese traditional medicine,has been reported to have anti-cancer activity.The purpose of this study was to examine the apoptotic activity of casticin on human cervical cancer cells and its molecular mechanism.We revealed a novel mechanism by which casticin-induced apoptosis occurs and showed for the first time that the apoptosis induced by casticin is mediated through generation of reactive oxygen species (ROS) and sustained activation of c-Jun N-terminal kinase (JNK) in HeLa cells.Casticin markedly increased the levels of intracellular ROS and induced the expression of phosphorylated JNK and cJun protein.Pre-treatment with N-acetylcvsteine and SP600125 effectively attenuated induction of apoptosis by casticin in HeLa cells.Moreover,casticin induced ROS production and apoptotic cell death in other cervical cancer cell lines,such as CasKi and SiHa.Importantly,casticin did not cause generation of ROS or induction of apoptosis in normal human peripheral blood mononuclear cells and embryonic kidney epithelium 293 cells.These results suggest that ROS generation and sustained JNK activation by casticin play a role in casticin-induced apoptosis and raise the possibility that treatment with casticin might be promising as a new therapy against human cervical cancer.

  17. Identification of differential anti-neoplastic activity of copper bis(thiosemicarbazones) that is mediated by intracellular reactive oxygen species generation and lysosomal membrane permeabilization.

    Stefani, Christian; Al-Eisawi, Zaynab; Jansson, Patric J; Kalinowski, Danuta S; Richardson, Des R

    2015-11-01

    Bis(thiosemicarbazones) and their copper (Cu) complexes possess unique anti-neoplastic properties. However, their mechanism of action remains unclear. We examined the structure-activity relationships of twelve bis(thiosemicarbazones) to elucidate factors regarding their anti-cancer efficacy. Importantly, the alkyl substitutions at the diimine position of the ligand backbone resulted in two distinct groups, namely, unsubstituted/monosubstituted and disubstituted bis(thiosemicarbazones). This alkyl substitution pattern governed their: (1) Cu(II/I) redox potentials; (2) ability to induce cellular (64)Cu release; (3) lipophilicity; and (4) anti-proliferative activity. The potent anti-cancer Cu complex of the unsubstituted bis(thiosemicarbazone) analog, glyoxal bis(4-methyl-3-thiosemicarbazone) (GTSM), generated intracellular reactive oxygen species (ROS), which was attenuated by Cu sequestration by a non-toxic Cu chelator, tetrathiomolybdate, and the anti-oxidant, N-acetyl-l-cysteine. Fluorescence microscopy suggested that the anti-cancer activity of Cu(GTSM) was due, in part, to lysosomal membrane permeabilization (LMP). For the first time, this investigation highlights the role of ROS and LMP in the anti-cancer activity of bis(thiosemicarbazones). PMID:26335599

  18. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  19. AMPK is Involved in Mediation of Erythropoietin Influence on Metabolic Activity and Reactive Oxygen Species Production in White Adipocytes

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

    2014-01-01

    Erythropoietin, discovered for its indispensable role during erythropoiesis, has been used in the therapy for selected red blood cell disorders in erythropoietin-deficient patients. The biological activities of erythropoietin have been found to extend to non-erythroid tissues due to the expression of erythropoietin receptor. We previously demonstrated that erythropoietin promotes metabolic activity and white adipocytes browning to increase mitochondrial function and energy expenditure via per...

  20. TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection.

    Jesus Segovia

    Full Text Available Human respiratory syncytial virus (RSV constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1β (IL-1β plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1β is synthesized as an immature pro-IL-1β form. It is cleaved by activated caspase-1 to yield mature IL-1β that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1β release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1β secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1β production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1β and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS and potassium (K(+ efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal and ROS/potassium efflux (second signal for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1β release during RSV infection.

  1. Ciglitazone induces apoptosis via activation of p38 MAPK and AIF nuclear translocation mediated by reactive oxygen species and Ca2+ in opossum kidney cells

    We have previously demonstrated that the synthetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist ciglitazone induces apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) and nuclear translocation of apoptosis inducing factor (AIF) in opossum kidney (OK) renal epithelial cells. However, the precise mechanism by which ciglitazone induces activation of p38 MAPK and the role of AIF in the induction of the apoptosis are not defined. This study was therefore undertaken to determine whether the roles of reactive oxygen species (ROS) generation and intracellular Ca2+ in the ciglitazone-induced activation of p38 MAPK and whether AIF nuclear translocation is responsible for the ciglitazone-induced apoptosis in OK renal epithelial cells. Ciglitazone caused generation of ROS and an increase in intracellular Ca2+. Ciglitazone-induced cell death was reduced by the antioxidant Trolox, the Ca2+ chelator EGTA, and the store-operated Ca2+ channels (SOCC) blocker lanthanum chloride (La3+), indicating involvement of ROS and Ca2+ in the ciglitazone-induced cell death. Ciglitazone-induced intracellular Ca2+ increase was decreased by Trolox, while ROS generation was not affected by EGTA and La3+, suggesting that ROS generation promote the increase of intracellular Ca2+. Transfection of small interfering RNA (siRNA) of p38 MAPK or vector expressing microRNA (miRNA) of AIF prevented the ciglitazone-induced cell death. Activation of p38 MAPK, mitochondrial membrane depolarization, and AIF nuclear translocation induced by ciglitazone were inhibited by Trolox, EGTA and La3+. Taken together, these results suggest that ROS-dependent intracellular Ca2+ increase is responsible for activation of p38 MAPK and nuclear translocation of AIF by ciglitazone

  2. Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action.

    Legault, Jean; Dahl, Wivecke; Debiton, Eric; Pichette, André; Madelmont, Jean-Claude

    2003-05-01

    The antitumor activity of the essential oil of Abies balsamea (balsam fir oil) was evaluated against several solid tumor cell lines including MCF-7, PC-3, A-549, DLD-1, M4BEU and CT-26. Balsam fir oil was found to be active against all the solid tumor cell lines tested, with GI 50 values ranging between 0.76 and 1.7 mg/mL. The oil was analyzed by GC-MS and the cytotoxicity of each oil constituent was determined. Balsam fir oil is essentially constituted of monoterpenes tau; 96 %) and some sesquiterpenes. All the compounds tested were inactive (tau; 250 microM) except for alpha-humulene (GI50 = 55 to 73 microM) which thus seems responsible for the cytotoxicity of the oil. We also tested the cytotoxicity of caryophyllene oxide, which proved inactive, and gamma-caryophyllene which was found to be active against all solid tumor cell lines tested. We evaluated the effects of balsam fir oil and alpha-humulene on the cellular glutathione (GSH) content and on the production of reactive oxygen species (ROS). Balsam fir oil and alpha-humulene induced a dose- and time-dependent decrease in cellular GSH content and an increase in ROS production. These results suggest that GSH depletion and ROS production may be implicated in the cytotoxicity of alpha-humulene and balsam fir oil. PMID:12802719

  3. Heat shock protein 27 regulates oxidative stress-induced apoptosis in cardiomyocytes:mechanisms via reactive oxygen species generation and Akt activation

    LIU Li; ZHANG Xiao-jin; JIANG Su-rong; DING Zheng-nian; DING Guo-xian; HUANG Jun; CHENG Yun-lin

    2007-01-01

    Background Increased reactive oxygen species(ROS)formation,which in turn promotes cardiomyocytes apoptosis,is associated with the pathogenesis and progression of various cardiac diseases such as ischemia and heart failure.Recent studies have shown that over expression of heat shock protein 27(Hsp27)confers resistance to cardiac ischemia/reperfusion injury.However,not much is known about the regulation of myocyte survival by Hsp27.Methods The rat cardiac cell line H9c2,with a stable overexpression of Hsp27,was established,with empty vector transfected H9c2 cells as controls.Following the cells challenged by Hydrogen Peroxide(H2O2),lactate dehydrogenase (LDH)release,apoptosis,intracellular ROS,cell morphology,mitochondrial transmembrane potential and the activation of serine/threonine kinase Akt were determined.Results Along with marked suppression of H2O2-induced injury by Hsp27 overexpression in H9c2 cells,ROS generation and the loss of mitochondrial membrane potential were also significantly depressed.Furthermore,augmented Akt activation was observed in Hsp27 overexpressed H9c2 cells following H2O2 exposure.Conclusions Hsp27 inhibits oxidative stress-induced H9c2 damage and inhibition of ROS generation and the augmentation of Akt activation may be involved in the protective signaling.

  4. Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

    Aaron C-H Chen; Arany, Praveen R.; Ying-Ying Huang; Tomkinson, Elizabeth M.; Sharma, Sulbha K.; Kharkwal, Gitika B.; Taimur Saleem; David Mooney; Yull, Fiona E.; Timothy S Blackwell; Hamblin, Michael R.

    2011-01-01

    BACKGROUND: Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: 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 NF-kB was observed at fluences higher than 0.003 J/cm(2) and was confirmed by Western blot ana...

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

    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

  6. Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes.

    Xiao, Fang; Li, Yanhong; Dai, Lu; Deng, Yuanyuan; Zou, Yue; Li, Peng; Yang, Yuan; Zhong, Caigao

    2012-09-01

    Hexavalent chromium [Cr(VI)], which is used for various industrial applications, such as leather tanning and chroming, can cause a number of human diseases including inflammation and cancer. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study provides evidence that Cr(VI) enhances reactive oxygen species (ROS) accumulation by inhibiting the mitochondrial respiratory chain complex (MRCC) I. Cr(VI) did not affect the expression levels of antioxidative proteins such as superoxide dismutase (SOD), catalase and thioredoxin (Trx), indicating that the antioxidative system was not involved in Cr(VI)-induced ROS accumulation. We found that ROS mediated caspase-3 activation partially depends on the downregulation of the heat shock protein (HSP) 70 and 90. In order to confirm our hypothesis that ROS plays a key role in Cr(VI)-mediated cytotoxicity, we used N-acetylcysteine (NAC) to inhibit the accumulation of ROS. NAC successfully blocked the inhibition of HSP70 and HSP90 as well as the activation of caspase-3, suggesting that ROS is essential in Cr(VI)-induced caspase-3 activation. By applying different MRCC substrates as electron donors, we also confirmed that Cr(VI) could accept the electrons leaked from MRCC I and the reduction occurs at MRCC I. In conclusion, the present study demonstrates that Cr(VI) induces ROS-dependent caspase-3 activation by inhibiting MRCC I activity, and MRCC I has been identified as a new target and a new mechanism for the apoptosis-inducing activity displayed by Cr(VI). PMID:22710416

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

    Yun, Hong Shik; Hong, Eun-Hee [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Su-Jae [Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Baek, Jeong-Hwa [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Yim, Ji-Hye; Um, Hong-Duck [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Hwang, Sang-Gu, E-mail: sgh63@kcch.re.kr [Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    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.

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

    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

  9. Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species

    Rajitha T Kolamunne

    2013-01-01

    Full Text Available Adaptive mechanisms involving upregulation of cytoprotective genes under the control of transcription factors such as Nrf2 exist to protect cells from permanent damage and dysfunction under stress conditions. Here we explore of the hypothesis that Nrf2 activation by reactive oxygen and nitrogen species modulates cytotoxicity during hypoxia (H with and without reoxygenation (H/R in H9C2 cardiomyoblasts. Using MnTBap as a cell permeable superoxide dismutase (SOD mimetic and peroxynitrite scavenger and L-NAME as an inhibitor of nitric oxide synthase (NOS, we have shown that MnTBap inhibited the cytotoxic effects of hypoxic stress with and without reoxygenation. However, L-NAME only afforded protection during H. Under reoxygenation, conditions, cytotoxicity was increased by the presence of L-NAME. Nrf2 activation was inhibited independently by MnTBap and L-NAME under H and H/R. The increased cytotoxicity and inhibition of Nrf2 activation by the presence of L-NAME during reoxygenation suggests that NOS activity plays an important role in cell survival at least in part via Nrf2-independent pathways. In contrast, O2−• scavenging by MnTBap prevented both toxicity and Nrf2 activation during H and H/R implying that toxicity is largely dependent on O2−·.To confirm the importance of Nrf2 for myoblast metabolism, Nrf2 knockdown with siRNA reduced cell survival by 50% during 4 h hypoxia with and without 2 h of reoxygenation and although cellular glutathione (GSH was depleted during H and H/R, GSH loss was not exacerbated by Nrf2 knockdown. These data support distinctive roles for ROS and RNS during H and H/R for Nrf2 induction which are important for survival independently of GSH salvage.

  10. Active oxygens and their protection

    Most of radiation-induced damages to living organisms are thought to be originated from active oxygens produced from water and oxygen in living organisms by irradiation. These active oxygens react with various intracellular components including DNA, proteins, lipids, carbohydrates and other lower molecular weight substances, then finally induce genetic damages, metabolic damages or abnormality of cell functions. Our studies demonstrated that active oxygens produced by radiation caused peroxidation of biological membrane lipids, resulting in destruction of membrane structure and inactivation of membrane-bound enzymes. The lipid peroxidation might be also one of the most important factors to induce radiation carcinogenesis. Protective substances in several rat tissues and yeast against active oxygens produced by radiation were also investigated and a basic protein which have high content of SH group and three different lower molecular weight substances were separated from rat liver cytosol. These substances have functions to suppress not only radiation-induced lipid peroxidation but also radiation-induced inactivation of membrane-bound enzymes. From these data, effect of active oxygens produced by radiation and their protection in organisms are discussed. (author)

  11. NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice.

    Qiu, Li-Li; Ji, Mu-Huo; Zhang, Hui; Yang, Jiao-Jiao; Sun, Xiao-Ru; Tang, Hui; Wang, Jing; Liu, Wen-Xue; Yang, Jian-Jun

    2016-01-01

    Microglial activation plays a key role in the development of postoperative cognitive dysfunction (POCD). Nox2, one of the main isoforms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the central nervous system, is a predominant source of reactive oxygen species (ROS) overproduction in phagocytes including microglia. We therefore hypothesized that Nox2-induced microglial activation is involved in the development of POCD. Sixteen-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery. Behavioral tests were performed at 6 and 7 d post-surgery with open field and fear conditioning tests, respectively. The levels of Nox2, 8-hydroxy-2'-deoxyguanosine (8-OH-dG, a marker of DNA oxidation), CD11b (a marker of microglial activation), interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) were determined in the hippocampus and prefrontal cortex at 1 d and 7 d post-surgery, respectively. For the interventional study, mice were treated with a NADPH oxidase inhibitor apocynin (APO). Our results showed that exploratory laparotomy with isoflurane anesthesia impaired the contextual fear memory, increased expression of Nox2, 8-OH-dG, CD11b, and IL-1β, and down-regulated BDNF expression in the hippocampus at 7 d post-surgery. The surgery-induced microglial activation and neuroinflammation persisted to 7 d after surgery in the hippocampus, but only at 1 d in the prefrontal cortex. Notably, administration with APO could rescue these surgery-induced cognitive impairments and associated brain pathology. Together, our data suggested that Nox2-derived ROS in hippocampal microglia, at least in part, contributes to subsequent neuroinflammation and cognitive impairments induced by surgery in aged mice. PMID:26254234

  12. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

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

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concent...

  13. [The two faces of reactive oxygen species].

    Zabłocka, Agnieszka; Janusz, Maria

    2008-01-01

    Oxidative stress has been implicated in playing a crucial role in aging and in the pathogeneses of a number of diseases, including neurodegenerative disorders such as Alzheimer's disease. Oxidative stress occurs due to an imbalance in prooxidant and antioxidant levels. Reactive oxygen species (ROS) are highly reactive and may modify and inactivate proteins, lipids, DNA, and RNA and induce cellular dysfunctions. To prevent free radical-induced cellular damage, the organism has developed a defense mechanism, the antioxidative system. This system includes antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and glutathione reductase (GSSGR) and low-molecular antioxidants such as glutathion and plasma proteins. Glutathion plays a key role in maintaining the physiological balance between prooxidants and antioxidants. Plasma proteins can inhibit ROS generation and lipid peroxidation by chelating free transition metals. The major exogenous antioxidants are vitamins E, C, and A. PMID:18388851

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

    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.

  15. Production and Consumption of Reactive Oxygen Species by Fullerenes

    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 ...

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

    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...

  17. Effect of chromium oxide (III) nanoparticles on the production of reactive oxygen species and photosystem II activity in the green alga Chlamydomonas reinhardtii.

    Costa, Cristina Henning da; Perreault, François; Oukarroum, Abdallah; Melegari, Sílvia Pedroso; Popovic, Radovan; Matias, William Gerson

    2016-09-15

    With the growth of nanotechnology and widespread use of nanomaterials, there is an increasing risk of environmental contamination by nanomaterials. However, the potential implications of such environmental contamination are hard to evaluate since the toxicity of nanomaterials if often not well characterized. The objective of this study was to evaluate the toxicity of a chromium-based nanoparticle, Cr2O3-NP, used in a wide diversity of industrial processes and commercial products, on the unicellular green alga Chlamydomonas reinhardtii. The deleterious impacts of Cr2O3-NP were characterized using cell density measurements, production of reactive oxygen species (ROS), esterase enzymes activity, and photosystem II electron transport as indicators of toxicity. Cr2O3-NP exposure inhibited culture growth and significantly lowered cellular Chlorophyll a content. From cell density measurements, EC50 values of 2.05±0.20 and 1.35±0.06gL(-1) Cr2O3-NP were obtained after 24 and 72h of exposure, respectively. In addition, ROS levels were increased to 160.24±2.47% and 59.91±0.15% of the control value after 24 and 72h of exposition to 10gL(-1) Cr2O3-NP. At 24h of exposure, the esterase activity increased to 160.24% of control value, revealing a modification of the short-term metabolic response of algae to Cr2O3-NP exposure. In conclusion, the metabolism of C. reinhardtii was the most sensitive to Cr2O3-NP after 24h of treatment. PMID:26803219

  18. Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation.

    Ki Sung Kang

    Full Text Available BACKGROUND: The present study sought to further investigate the in vitro and in vivo anticancer effects of a representative omega-3 fatty acid, docosahexaenoic acid (DHA, with a focus on assessing the induction of oxidative stress and apoptosis as an important mechanism for its anticancer actions. METHODOLOGY/PRINCIPAL FINDINGS: In vitro studies showed that DHA strongly reduces the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and also promotes cell death via apoptosis. Mechanistically, accumulation of reactive oxygen species and activation of caspase 8 contribute critically to the induction of apoptotic cell death. Co-presence of antioxidants or selective inhibition or knockdown of caspase 8 each effectively abrogates the cytotoxic effect of DHA. Using athymic nude mice as an in vivo model, we found that feeding animals the 5% fish oil-supplemented diet for 6 weeks significantly reduces the growth of MCF-7 human breast cancer cells in vivo through inhibition of cancer cell proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that the fish oil-supplemented diet significantly increases oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and tissues showed that feeding animals a 5% fish oil diet increases the levels of DHA and eicosapentaenoic acid in both normal and tumorous mammary tissues by 329% and 300%, respectively. CONCLUSIONS/SIGNIFICANCE: DHA can strongly induce apoptosis in human MCF-7 breast cancer cells both in vitro and in vivo. The induction of apoptosis in these cells is selectively mediated via caspase 8 activation. These observations call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of human breast cancer.

  19. Homeopathic mother tincture of Phytolacca decandra induces apoptosis in skin melanoma cells by activating caspase-mediated signaling via reactive oxygen species elevation

    Samrat Ghosh; Kausik Bishayee; Avijit Paul; Avinaba Mukherjee; Sourav Sikdar; Debrup Chakraborty; Naoual Boujedaini

    2013-01-01

    OBJECTIVE:Preventive measures against skin melanoma like chemotherapy are useful but suffer from chronic side effects and drug resistance.Ethanolic extract of Phytolacca decandra (PD),used in homeopathy for the treatment of various ailments like chronic rheumatism,regular conjunctivitis,psoriasis,and in some skin diseases was tested for its possible anticancer potential.METHODS:Cytotoxicity of the drug was tested by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on both normal (peripheral blood mononuclear cells) and A375 cells.Fluorescence microscopic study of 4',6-diamidino-2-phenylindole dihydrochloride-stained cells was conducted for DNA fragmentation assay,and changes in cellular morphology,if any,were also recorded.Lactate dehydrogenase activity assay was done to evaluate the percentages of apoptosis and necrosis.Reactive oxygen species (ROS) accumulation,if any,and expression study of apoptotic genes also were evaluated to pin-point the actual events of apoptosis.RESULTS:Results showed that PD administration caused a remarkable reduction in proliferation of A375 cells,without showing much cytotoxicity on peripheral blood mononuclear cells.Generation of ROS and DNA damage,which made the cancer cells prone to apoptosis,were found to be enhanced in PD-treated cells.These results were duly supported by the analytical data on expression of different cellular and nuclear proteins,as for example,by downregulation of Akt and Bcl-2,up-regulation of p53,Bax and caspase 3,and an increase in number of cell deaths by apoptosis in A375 cells.CONCLUSION:Overall results demonstrate anticancer potentials of PD on A375 cells through activation of caspase-mediated signaling and ROS generation.

  20. CARRAGEENAN-INDUCED NFκB ACTIVATION DEPENDS ON DISTINCT PATHWAYS MEDIATED BY REACTIVE OXYGEN SPECIES AND HSP27 OR BY BCL10

    Bhattacharyya, Sumit; Dudeja, Pradeep K.; Tobacman, Joanne K.

    2013-01-01

    Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/lymphoma 10). However, increases in phospho-IκBα and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NFκB (p65), phospho-IκBα, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38γ), MAPK 13 (p38δ), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the IκBα kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKKγ (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome. PMID:18452717

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

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

    2012-01-01

    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 t...

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

    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

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

    Zhou, Limin; Huang, Yujie; Zhang, Yingying [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China); Zhao, Qingwei [The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79, Qing Chun Road, Hangzhou 310003 (China); Zheng, Bei; Lou, Yijia [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China); Zhu, Danyan, E-mail: zdyzxb@zju.edu.cn [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, No. 866, Yu Hang Tang Road, Hangzhou 310058 (China)

    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

    Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States); School of Dentistry and Institute of Oral Biosciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States)

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

    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

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

    Zhao Jingxia [Nankai University, College of Medicine (China); Yao Yang [Tianjin First Central Hospital (China); Liu Shichang [Nankai University, College of Medicine (China); Zhang Tao [Nankai University, College of Life Science (China); Ren Guogang [University of Hertfordshire, Science and Technology Research Institute (United Kingdom); Yang Zhuo, E-mail: zhuoyang@nankai.edu.cn [Nankai University, College of Medicine (China)

    2012-11-15

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

  7. Endothelin-2/Vasoactive Intestinal Contractor: Regulation of Expression via Reactive Oxygen Species Induced by CoCl22, and Biological Activities Including Neurite Outgrowth in PC12 Cells

    Eiichi Kotake-Nara

    2006-01-01

    Full Text Available This paper reviews the local hormone endothelin-2 (ET-2, or vasoactive intestinal contractor (VIC, a member of the vasoconstrictor ET peptide family, where ET-2 is the human orthologous peptide of the murine VIC. While ET-2/VIC gene expression has been observed in some normal tissues, ET-2 recently has been reported to act as a tumor marker and as a hypoxia-induced autocrine survival factor in tumor cells. A recently published study reported that the hypoxic mimetic agent CoCl2 at 200 µM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced intracellular reactive oxygen species (ROS increase and neurite outgrowth in neuronal model PC12 cells. The ROS was generated by addition of CoCl2 to the culture medium, and the CoCl2-induced effects were completely inhibited by the antioxidant N-acetyl cysteine. Furthermore, interleukin-6 (IL-6 gene expression was up-regulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by CoCl2-induced ROS may be associated with neuronal differentiation through the regulation of IL-6 expression. CoCl2 acts as a pro-oxidant, as do Fe(II, III and Cu(II. However, some biological activities have been reported for CoCl2 that have not been observed for other metal salts such as FeCl3, CuSO4, and NiCl2. The characteristic actions of CoCl2 may be associated with the differentiation of PC12 cells. Further elucidation of the mechanism of neurite outgrowth and regulation of ET-2/VIC expression by CoCl2 may lead to the development of treatments for neuronal disorders.

  8. Reducing Cytoplasmic Polyamine Oxidase Activity in Arabidopsis Increases Salt and Drought Tolerance by Reducing Reactive Oxygen Species Production and Increasing Defense Gene Expression.

    Sagor, G H M; Zhang, Siyuan; Kojima, Seiji; Simm, Stefan; Berberich, Thomas; Kusano, Tomonobu

    2016-01-01

    The link between polyamine oxidases (PAOs), which function in polyamine catabolism, and stress responses remains elusive. Here, we address this issue using Arabidopsis pao mutants in which the expression of the five PAO genes is knocked-out or knocked-down. As the five single pao mutants and wild type (WT) showed similar response to salt stress, we tried to generate the mutants that have either the cytoplasmic PAO pathway (pao1 pao5) or the peroxisomal PAO pathway (pao2 pao3 pao4) silenced. However, the latter triple mutant was not obtained. Thus, in this study, we used two double mutants, pao1 pao5 and pao2 pao4. Of interest, pao1 pao5 mutant was NaCl- and drought-tolerant, whereas pao2 pao4 showed similar sensitivity to those stresses as WT. To reveal the underlying mechanism of salt tolerance, further analyses were performed. Na uptake of the mutant (pao1 pao5) decreased to 75% of WT. PAO activity of the mutant was reduced to 62% of WT. The content of reactive oxygen species (ROS) such as hydrogen peroxide, a reaction product of PAO action, and superoxide anion in the mutant became 81 and 72% of the levels in WT upon salt treatment. The mutant contained 2.8-fold higher thermospermine compared to WT. Moreover, the mutant induced the genes of salt overly sensitive-, abscisic acid (ABA)-dependent- and ABA-independent- pathways more strongly than WT upon salt treatment. The results suggest that the Arabidopsis plant silencing cytoplasmic PAOs shows salinity tolerance by reducing ROS production and strongly inducing subsets of stress-responsive genes under stress conditions. PMID:26973665

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

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

  10. Hyperglycemia Enhances IGF-I–Stimulated Src Activation via Increasing Nox4-Derived Reactive Oxygen Species in a PKCζ-Dependent Manner in Vascular Smooth Muscle Cells

    Xi, Gang; Shen, Xinchun; Maile, Laura A.; Wai, Christine; Gollahon, Katherine; Clemmons, David R.

    2011-01-01

    IGF-I–stimulated sarcoma viral oncogene (Src) activation during hyperglycemia is required for propagating downstream signaling. The aim of the current study was to determine the mechanism by which hyperglycemia enhances IGF-I–stimulated Src activation and the role of NADPH oxidase 4 (Nox4) and protein kinase C ζ (PKCζ) in mediating this response in vascular smooth muscle cells (VSMCs). Nox4 expression was analyzed in VSMCs exposed to hyperglycemia. The role of Nox4-derived reactive oxygen spe...

  11. Reactive oxygen species and anti-proteinases.

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

    2016-01-01

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

  12. Structurally related antitumor effects of flavanones in vitro and in vivo: involvement of caspase 3 activation, p21 gene expression, and reactive oxygen species production

    Flavonoids exist extensively in plants and Chinese herbs, and several biological effects of flavonoids have been demonstrated. The antitumor effects in colorectal carcinoma cells (HT29, COLO205, and COLO320HSR) of eight flavanones including flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone, 7-OH flavanone, naringenin, nargin, and taxifolin were investigated. Results of the MTT assay indicate that 2'-OH flavanone showed the most potent cytotoxic effect on these three cells, and cell death induced by 2'-OH flavanone was via the occurrence of DNA ladders, apoptotic bodies, and hypodiploid cells, all characteristics of apoptosis. Induction of caspase 3 protein processing and enzyme activity associated with cleavage of poly(ADP-ribose) polymerase (PARP) was identified in 2'-OH flavanone-treated cells, and a peptidyl inhibitor (Ac-DEVD-FMK) of caspase 3 attenuated the cytotoxicity of 2'-OH flavanone in COLO205 and HT-29 cells. Elevation of p21 (but not p53) and a decrease in Mcl-1 protein were found in 2'-OH flavanone-treated COLO205 and HT-29 cells. Elevation of intracellular reactive oxygen species (ROS) was detected in 2'-OH flavanone-treated cells by the 2',7'-dichlorodihydrofluorescein diacetate (DCHF-DA) assay, and ROS scavengers including 4,5-dihydro-1,3-benzene disulfonic acid (tiron), catalase, superoxide dismutase (SOD), and pyrrolidine dithiocarbamate (PDTC) suppressed the 2'-OH flavanone-induced cytotoxic effect. Subcutaneous injection of COLO205 induced tumor formation in nude mice, and 2'-OH flavanone showed a significant inhibitory effect on tumor formation. The appearance of apoptotic cells with H and E staining, and an increase in p21, but not p53, protein by immunohistochemistry were observed in tumor tissues under 2'-OH flavanone treatment. Primary tumor cells (COLO205-X) derived from a tumor specimen elicited by COLO205 were established, and 2'-OH flavanone showed an significant apoptotic effect in COLO205-X cells in accordance with the

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

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

    2013-01-01

    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...

  14. Combined application of XANES and XPS to study oxygen species adsorbed on Ag foil

    Bukhtiyarov, V I; Kaichev, V V; Knop-Gericke, A; Mayer, R W; Schloegl, R

    2001-01-01

    Adsorbed oxygen species realized in the course of ethylene epoxidation over polycrystalline silver have been characterized by X-ray absorption near the edge structure and X-ray photoelectron spectroscopy. Namely, the combined application of XANES and XPS in similar UHV conditions using the same sample allowed us to assign an XAS feature to the nucleophilic and electrophilic oxygen. This is of great significance, since these species are suggested to be included into the active center for ethylene epoxidation. The differences in the oxygen-silver bonding of these oxygen species are discussed.

  15. Effects of signal transducer and activator of transcription 3 RNAi on content of reactive oxygen species and DNA damage in glioma cell

    Objective: To investigate the effects of signal transducer and activator of transcription 3 (STAT3) RNAi on the content of reactive oxygen species (ROS) and the DNA damage in glioma cells. Methods: Glioma cells of the line U251 cells were cultured and transfected with STAT3 RNAi plasmid (pSilencer2.1-STAT3, STAT3 group) and pSilencer2.1-GFP (GFP control group) respectively. Part of the U251 cells were irradiated with γ-rays of 60Co as positive control group of smear phenomenon. The levels of ROS and malondialdehyde (MDA) in the cells were detected 24, 48, and 72 h later by flow cytometry and fluorescence chamoluminescence analyzer, respectively. The DNA damage in the transfected U251 cells was examined by using single cell gel electrophoresis assay, and the cell cycle distribution was examined using FACS PI staining 12, 24, and 36 h later. Results: At 24 h after the transfection, the ROS level of the siSTAT3-transfected cells was 8.91 times that of the control group (F=89.296, P<0.05), and returned to the normal level 48 h later. There were not significant differences in the MDA level of the cells 24, 48, and 72 h later between the siSTAT3 group and siGFP group. Compared with the 8 Gy irradiation positive group with obvious smear phenomenon, smear phenomenon was shown in part of the cells in the siSTAT3 group 6 h later, became less 12 h later, and disappeared completely 24 h later. Compared with the control group,lag of S stage rate was 17.22% and the lag of G2/M stage rate was 6.4% 12 h later in the siSTAT-transfected group,and the G0/G1 stage lag rate was 18.44% 24 h later, and the lag of S stage rate was 17.99% 36 h later. Conclusions: Inhibition of STAT3 results in the change of oxido reduction status in glioma cells, as well as damage and reparation of DNA. (authors)

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

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

    2011-06-01

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

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

    Anantha eHarijith

    2014-09-01

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

  18. Mitochondrial-targeted fluorescent probes for reactive oxygen species

    Dickinson, Bryan C; Srikun, Duangkhae; Chang, Christopher J.

    2009-01-01

    As the primary consumers of oxygen within all aerobic organisms, mitochondria are a major source of cellular reactive oxygen species (ROS) derived from the in vivo chemistry of oxygen metabolism. Mitochondrial ROS have been traditionally implicated in aging and in a variety of pathologies, including cancer, neurodegeneration, and diabetes, but recent studies also link controlled mitochondrial ROS fluxes to cell regulation and signaling events. Progress in the development of mitochondrial-targ...

  19. Production and Detection of Reactive Oxygen Species (ROS) in Cancers

    Wu, Danli; Yotnda, Patricia

    2011-01-01

    Reactive oxygen species include a number of molecules that damage DNA and RNA and oxidize proteins and lipids (lipid peroxydation). These reactive molecules contain an oxygen and include H2O2 (hydrogen peroxide), NO (nitric oxide), O2- (oxide anion), peroxynitrite (ONOO-), hydrochlorous acid (HOCl), and hydroxyl radical (OH-).

  20. TNF α and reactive oxygen species in necrotic cell death

    Michael J Morgan; You-Sun Kim; Zheng-gang Liu

    2008-01-01

    Death receptors, including the TNF receptor-1 (TNF-RI), have been shown to be able to initiate caspase-independent cell death. This form of "necrotic cell death" appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNFa and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNFa indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells.

  1. Determination of intracellular reactive oxygen species and high mitochondrial membrane potential in Percoll-treated viable boar sperm using fluorescence-activated flow cytometry.

    Guthrie, H D; Welch, G R

    2006-08-01

    The use of frozen semen in the swine industry is limited by problems with viability and fertility compared with liquid semen. Part of the reduction in sperm motility and fertility associated with cryopreservation may be due to oxidative damage from excessive or inappropriate formation of reactive oxygen species (ROS). Chemiluminescence measurements of ROS are not possible in live cells and are problematic because of poor specificity. An alternative approach, flow cytometry, was developed to identify viable boar sperm containing ROS utilizing the dyes hydroethidine and 2', 7'-dichlorodihydrofluorescein diacetate as oxidizable substrates and impermeant DNA dyes to exclude dead sperm. The percentage of sperm with high mitochondrial transmembrane potential was determined by flow cytometry using the mitochondrial probe 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolylcarbocyanine iodide with propidium iodide staining to exclude nonviable cells. Sperm were incubated with and without ROS generators and free radical scavengers. Basal ROS formation was low (less than 4%) and did not differ (P = 0.26) between viable fresh and frozen-thawed boar sperm. In addition, fresh and frozen-thawed viable sperm were equally susceptible (P = 0.20) to intracellular formation of ROS produced by xanthine/xanthine oxidase (94.4 and 87.9% of sperm, respectively). Menadione increased (P boar sperm, both were quite susceptible to external sources of hydrogen peroxide. PMID:16864869

  2. Reactive oxygen species (ROS) production triggered by prostaglandin D2 (PGD2) regulates lactate dehydrogenase (LDH) expression/activity in TM4 Sertoli cells.

    Rossi, Soledad P; Windschüttl, Stefanie; Matzkin, María E; Rey-Ares, Verónica; Terradas, Claudio; Ponzio, Roberto; Puigdomenech, Elisa; Levalle, Oscar; Calandra, Ricardo S; Mayerhofer, Artur; Frungieri, Mónica B

    2016-10-15

    Reactive oxygen species (ROS) regulate testicular function in health and disease. We previously described a prostaglandin D2 (PGD2) system in Sertoli cells. Now, we found that PGD2 increases ROS and hydrogen peroxide (H2O2) generation in murine TM4 Sertoli cells, and also induces antioxidant enzymes expression suggesting that defense systems are triggered as an adaptive stress mechanism that guarantees cell survival. ROS and specially H2O2 may act as second messengers regulating signal transduction pathways and gene expression. We describe a stimulatory effect of PGD2 on lactate dehydrogenase (LDH) expression via DP1/DP2 receptors, which is prevented by the antioxidant N-acetyl-L-cysteine and the PI3K/Akt pathway inhibitor LY 294002. PGD2 also enhances Akt and CREB/ATF-1 phosphorylation. Our results provide evidence for a role of PGD2 in the regulation of the oxidant/antioxidant status in Sertoli cells and, more importantly, in the modulation of LDH expression which takes place through ROS generation and the Akt-CREB/ATF-1 pathway. PMID:27329155

  3. Direct observation of the oxygenated species during oxygen reduction on a platinum fuel cell cathode

    Kaya, Sarp; Casalongue, Hernan Sanchez; Viswanathan, Venkatasubramanian ; Miller, Daniel J. ; Friebel, Daniel ; Hansen, Heine A. ; Nørskov, Jens K. ; Nilsson, Anders ; Ogasawara, Hirohito

    2013-01-01

    The performance of polymer electrolyte membrane fuel cells is limited by the reduction at the cathode of various oxygenated intermediates in the four-electron pathway of the oxygen reduction reaction. Here we use ambient pressure X-ray photoelectron spectroscopy, and directly probe the correlation between the adsorbed species on the surface and the electrochemical potential. We demonstrate that, during the oxygen reduction reaction, hydroxyl intermediates on the cathode surface occur in sever...

  4. 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.

    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. PMID:26319994

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

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

    2014-03-01

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

  6. Mechanisms of nanotoxicity: Generation of reactive oxygen species

    Peter P. Fu

    2014-03-01

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

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

    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.

  8. Enhanced expression of WD repeat-containing protein 35 (WDR35 stimulated by domoic acid in rat hippocampus: involvement of reactive oxygen species generation and p38 mitogen-activated protein kinase activation

    Tsunekawa Koji

    2013-01-01

    Full Text Available Abstract Background Domoic acid (DA is an excitatory amino acid analogue of kainic acid (KA that acts via activation of glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown to elicit reactive oxygen species (ROS production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK in vitro. We have reported that WDR35, a WD-repeat protein, may mediate apoptosis in several animal models. In the present study, we administered DA to rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS to identify and quantify DA in the brains of the rats and performed histological examinations of the hippocampus. We further investigated the potential involvement of glutamate receptors, ROS, p38 MAPK, and WDR35 in DA-induced toxicity in vivo. Results Our results showed that intraperitoneally administered DA was present in the brain and induced neurodegenerative changes including apoptosis in the CA1 region of the hippocampus. DA also increased the expression of WDR35 mRNA and protein in a dose- and time-dependent manner in the hippocampus. In experiments using glutamate receptor antagonists, the AMPA/KA receptor antagonist NBQX significantly attenuated the DA-induced increase in WDR35 protein expression, but the NMDA receptor antagonist MK-801 did not. In addition, the radical scavenger edaravone significantly attenuated the DA-induced increase in WDR35 protein expression. Furthermore, NBQX and edaravone significantly attenuated the DA-induced increase in p38 MAPK phosphorylation. Conclusion In summary, our results indicated that DA activated AMPA/KA receptors and induced ROS production and p38 MAPK phosphorylation, resulting in an increase in the expression of WDR35 in vivo.

  9. Properties of Reactive Oxygen Species by Quantum Monte Carlo

    Zen, Andrea; Guidoni, Leonardo

    2014-01-01

    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 ...

  10. Kinetics of reactive oxygen species produced by rainbow trout (Oncorhynchus mykiss) leukocytes and the effect of the antioxidant astaxanthin

    Gómez, L; Cortés, Raúl; Valenzuela, A.; Smith, C. T.

    2014-01-01

    Reactive oxygen species contribute to kill of microorganisms. Their activity is usually measured by their capacity to reduce nitroblue tetrazolium into formazan. The incubation time to allow nitroblue tetrazolium reduction by reactive oxygen species usually ranges from 30 to 60 min. The aim of our study was to determine the kinetics of formazan formation, to determine the shortest incubation time possible, and to find if astaxanthin negatively affects the availability of reactive oxygen speci...

  11. Enrofloxacin drug induced reactive oxygen species

    Ishraga G. Ibrahim; Yarsan E

    2011-01-01

    Fluroquinolones drugs are known to have adverse effects including chondriotoxicity, however, the mechanism of this effect was not fully understood. To investigate the possibility of the involvement of oxidative stress in this mechanism, enrofloxacin was administered orally to 80 broiler chicks for 15 and 30 days at 100, 200 and 400 mg/kg body weight and the activities of some antioxidant enzymes and malondialdehide (MDA) blood levels were studied. An increase in MDA levels and decrease in the...

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

    Cordeiro, Rodrigo M

    2014-01-01

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

  13. A role for reactive oxygen species in postharvest biocontrol

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

  14. Reactive oxygen species in cancer: a dance with the devil.

    Schumacker, Paul T

    2015-02-01

    Reactive oxygen species (ROS) can initiate cancer, but oxidant generation in tumors leaves them vulnerable to further stresses. In this issue of Cancer Cell, Harris and colleagues show that augmenting oxidant stress in normal cells limits tumor initiation and progression. Hence, strategic targeting of antioxidant systems may undermine survival of new tumor cells. PMID:25670075

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

    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.

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

    Highlights: ► Matairesinol suppresses mitochondrial ROS generation during hypoxia. ► Matairesinol exhibits potent anti-angiogenic activity both in vitro and in vivo. ► 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-1α in hypoxic HeLa cells. These results demonstrate that matairesinol could function as a novel angiogenesis inhibitor by suppressing mROS signaling.

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

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

    2012-04-27

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

  18. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    Lun Zhang

    2016-01-01

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

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

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

    2014-04-01

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

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

    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.

  1. Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes.

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2016-06-01

    The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts. PMID:26951232

  2. Properties of reactive oxygen species by quantum Monte Carlo

    Zen, Andrea [Dipartimento di Fisica, La Sapienza - Università di Roma, Piazzale Aldo Moro 2, 00185 Rome (Italy); Trout, Bernhardt L. [Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, Massachusetts 02139 (United States); Guidoni, Leonardo, E-mail: leonardo.guidoni@univaq.it [Dipartimento di Scienze Fisiche e Chimiche, Università degli studi de L' Aquila, Via Vetoio, 67100 Coppito, L' Aquila (Italy)

    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.

  3. Efficient oxygen electrocatalysis on special active sites

    Halck, Niels Bendtsen

    cobalt incorporated in ruthenium dioxide at high overpotentials during the oxygen reduction reaction (ORR). Density functional theory calculations were used to explain this phenomenon. The special active sites concepts are used to propose a general unified approach to increase the efficiency for oxygen...

  4. Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelia induces apoptosis by increasing intracellular calcium levels and activating JNK and NADPH oxidase-dependent generation of reactive oxygen species.

    Tae Hwan Kim

    Full Text Available Khz is a compound derived from the fusion of Ganoderma lucidum and Polyporus umbellatus mycelia that inhibits the growth of cancer cells. The results of the present study show that Khz induced apoptosis preferentially in transformed cells and had only minimal effects on non-transformed cells. Furthermore, Khz induced apoptosis by increasing the intracellular Ca(2+ concentration ([Ca(2+](i and activating JNK to generate reactive oxygen species (ROS via NADPH oxidase and the mitochondria. Khz-induced apoptosis was caspase-dependent and occurred via a mitochondrial pathway. ROS generation by NADPH oxidase was critical for Khz-induced apoptosis, and although mitochondrial ROS production was also required, it appeared to occur secondary to ROS generation by NADPH oxidase. Activation of NADPH oxidase was demonstrated by the translocation of regulatory subunits p47(phox and p67(phox to the cell membrane and was necessary for ROS generation by Khz. Khz triggered a rapid and sustained increase in [Ca(2+](i, which activated JNK. JNK plays a key role in the activation of NADPH oxidase because inhibition of its expression or activity abrogated membrane translocation of the p47(phox and p67(phox subunits and ROS generation. In summary, these data indicate that Khz preferentially induces apoptosis in cancer cells, and the signaling mechanisms involve an increase in [Ca(2+](i, JNK activation, and ROS generation via NADPH oxidase and mitochondria.

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

    Rajeshwary Ghosh

    2015-01-01

    Full Text Available 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.

  6. Reactive oxygen species promote raft formation in T lymphocytes.

    Lu, Shu-Ping; Lin Feng, Ming-Hsien; Huang, Huey-Lan; Huang, Ya-Ching; Tsou, Wen-I; Lai, Ming-Zong

    2007-04-01

    Lipid rafts are involved in many cell biology events, yet the molecular mechanisms on how rafts are formed are poorly understood. In this study we probed the possible requirement of reactive oxygen species (ROS) for T-cell receptor (TCR)-induced lipid raft formation. Microscopy and biochemical analyses illustrated that blockage of ROS production, by superoxide dismutase-mimic MnTBAP, significantly reduced partitioning of LAT, phospho-LAT, and PLC-gamma in lipid rafts. Another antioxidant N-acetylcysteine (NAC) displayed a similar suppressive effect on the entry of phospho-LAT into raft microdomains. The involvement of ROS in TCR-mediated raft assembly was observed in T-cell hybridomas, T leukemia cells, and normal T cells. Removal of ROS was accompanied by an attenuated activation of LAT and PKCtheta, with reduced production of IL-2. Consistently, treating T cells with the ROS-producer tert-butyl hydrogen peroxide (TBHP) greatly enhanced membrane raft formation, distribution of phospho-LAT into lipid rafts, and increased IL-2 production. Our results indicate for the first time that ROS contribute to TCR-induced membrane raft formation. PMID:17349922

  7. Role of reactive oxygen species in the renal fibrosis

    NIE Jing; HOU Fan-fan

    2012-01-01

    Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology.Accumulating evidence indicates that oxidative stress,resulting in generation of reactive oxygen species (ROS),plays a critical role in the initiation and progression of fibrotic diseases.Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease.Multiple stimuli and agonists,such as transforming growth factor β1,tumor necrosis factor,platelet derived growth factor,angiotensin Ⅱ,hyperglycemia,oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production.ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products (AOPPs) and advanced glycation end products,which are not only markers of oxidative stress but also cause renal injury.Targeting NADPH oxidase and/or reducing AOPPs production might be a novel strategy for the therapeutic intervention of variety of fibrotic kidney disorders.

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

    Babatunji Emmanuel Oyinloye

    2015-04-01

    Full Text Available 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.

  9. 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 Cells1

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

    2002-01-01

    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. PMID:12376637

  10. Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria.

    Misra, Hari S; Khairnar, Nivedita P; Barik, Atanu; Indira Priyadarsini, K; Mohan, Hari; Apte, Shree K

    2004-12-01

    Transgenic Escherichia coli expressing pyrroloquinoline-quinone (PQQ) synthase gene from Deinococcus radiodurans showed superior survival during Rose Bengal induced oxidative stress. Such cells showed significantly low levels of protein carbonylation as compared to non-transgenic control. In vitro, PQQ reacted with reactive oxygen species with rate constants comparable to other well known antioxidants, producing non-reactive molecular products. PQQ also protected plasmid DNA and proteins from the oxidative damage caused by gamma-irradiation in solution. The data suggest that radioprotective/oxidative stress protective ability of PQQ in bacteria may be consequent to scavenging of reactive oxygen species per se and induction of other free radical scavenging mechanism. PMID:15581610

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

    Vallyathan, V; Shi, X.; Castranova, V.

    1998-01-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. ...

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

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

    2008-01-01

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

  13. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    Khan, Saeed R.

    2014-01-01

    Calcium oxalate (CaOx) kidney stones are formed attached to Randall’s plaques (RPs) or Randall’s plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in sup...

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

    Jenkins, Noah C.; Douglas Grossman

    2013-01-01

    We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of ...

  15. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

    Gonçalves, Renata L. S.; Oliveira, Jose Henrique M.; Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Pedro L Oliveira; Barillas-Mury, Carolina

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses ...

  16. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    Subhashini Bolisetty

    2013-03-01

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

  17. Radioadaptive response viewed from the relationship with reactive oxygen species and anti oxidative cellular capability

    Radiation-induced adaptive response (PAR) is a phenomenon manifesting as a priming low dose-induced resistance against a subsequent irradiation at higher dose. To understand this biological defensive phenomenon against radiation, it is important to study from the mechanistic point of view of two basic aspects: One is the antioxidative capability to scavenge the reactive oxygen species generated by radiation, and the other is the capability to repair radiation-induced damages. In this review, we summarize the knowledge of reactive oxygen species, and discuss the relationship between the low dose-induced increase in antioxidative activity and PAR. (author)

  18. Vitiligo, reactive oxygen species and T-cells.

    Glassman, Steven J

    2011-02-01

    The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo. PMID

  19. Imbalance in the enzymatic system of production and consumption of active oxygen species in liver of AKR mice with spontaneous leucosis.

    Vartanyan, L S; Gurevich, S M; Kozachenko, A I; Nagler, L G; Burlakova, E B

    2001-07-01

    Activities of protective antioxidant enzymes, the rate of superoxide formation (v) in microsomal membranes and submitochondrial particles (SMP), and the concentrations of reduced and oxidized glutathione in cytosol were studied in the liver of AKR mice during the development of spontaneous leucosis. It was found that in the latent period of leucosis (mice of 3-6 months of age) the glutathione reductase (GR) activity in cytosol and mitochondria decreased and v in SMP increased. The increase in v in SMP did not result in the induction of Mn-SOD. In this stage of leucosis, the activities of Cu,Zn-SOD, GSH-Px, and G-6-PDH in cytosol were unchanged; at the same time, the GR activity and the concentration of reduced glutathione smoothly decreased. In the stage of developed leucosis (mice of 7-9 months of age), non-synchronous changes in the antioxidant system resulting in the shift of metabolism towards the prooxidant state were found. Comparison of our findings and the literature data demonstrates that the observed decrease in the SOD/GSH-Px ratio, the decrease in GR activity, and the increase in the v/Mn-SOD activity ratio are typical for pre-neoplastic changes in cell metabolism. PMID:11563951

  20. Osthole regulates inflammatory mediator expression through modulating NF-κB, mitogen-activated protein kinases, protein kinase C, and reactive oxygen species.

    Liao, Pei-Chun; Chien, Shih-Chang; Ho, Chen-Lung; Wang, Eugene I-Chen; Lee, Shu-Ching; Kuo, Yueh-Hsiung; Jeyashoke, Narumon; Chen, Jie; Dong, Wei-Chih; Chao, Louis Kuoping; Hua, Kuo-Feng

    2010-10-13

    Osthole, a coumarin compound, has been reported to exhibit various biological activities; however the cellular mechanism of its immune modulating activity has not yet been fully addressed. In this study we isolated osthole from the seeds of Cnidium monnieri and demonstrated that osthole inhibited TNF-α, NO and COX-2 expression in LPS-stimulated macrophages, without reducing the expression of IL-6. Furthermore, the phosphorylation of p38, JNK1/2, PKC-α and PKC-ε induced by LPS was inhibited by osthole; however, the phosphorylation of ERK1/2 and PKC-δ was not reduced by osthole. Osthole also inhibited NF-κB activation and ROS release in LPS-stimulated macrophages. Our current results indicated that osthole is the major anti-inflammatory ingredient of Cnidium monnieri seed ethanol extract. PMID:20839800

  1. 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.

    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. PMID:27312204

  2. Implications for reactive oxygen species in schizophrenia pathogenesis.

    Koga, Minori; Serritella, Anthony V; Sawa, Akira; Sedlak, Thomas W

    2016-09-01

    Oxidative stress is a well-recognized participant in the pathophysiology of multiple brain disorders, particularly neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. While not a dementia, a wide body of evidence has also been accumulating for aberrant reactive oxygen species and inflammation in schizophrenia. Here we highlight roles for oxidative stress as a common mechanism by which varied genetic and epidemiologic risk factors impact upon neurodevelopmental processes that underlie the schizophrenia syndrome. While there is longstanding evidence that schizophrenia may not have a single causative lesion, a common pathway involving oxidative stress opens the possibility for intervention at susceptible phases. PMID:26589391

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

    Guterres, Fernanda Augusta de Lima Barbosa; Martinez, Glaucia Regina; Rocha, Maria Eliane Merlin; Winnischofer, Sheila Maria Brochado, E-mail: sheilambw@ufpr.br

    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.

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

    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

  5. Efficient oxygen electrocatalysis on special active sites

    Halck, Niels Bendtsen

    Oxygen electrocatalysis will be pivotal in future independent of fossil fuels. Renewable energy production will rely heavily on oxygen electrocatalysis as a method for storing energy from intermittent energy sources such as the wind and sun in the form of chemical bonds and to release the energy ...... electrocatalysis (ORR and OER) using organic functional groups on another class of catalysts. These consist of graphene sheets modified to have a local porphyrine site with different transition metals ions as model systems....... stored in these bonds in an eco-friendly fashion in fuel cells. This thesis explores catalysts for oxygen electrocatalysis and how carefully designed local structures on catalysts surfaces termed special active sites can influence the activity. Density functional theory has been used as a method...... throughout this thesis to understand these local structure effects and their influence on surface reactions. The concept of these special active sites is used to explain how oxygen evolution reaction (OER) catalysts can have activities beyond the limits of what was previously thought possible. The concept is...

  6. Study of the photochemically generated of oxygen species by fullerene photosensitized CoS2 nanocompounds

    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. • C60 has good effect during the photo-degradation processes. • Photocatalytic activity attributed to photo-absorption effect by C60 and cooperative effect of CoS2. - 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, CoS2 and CoS2–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 CoS2 and fullerene nanoparticles, the photochemically effect of the fullerene photosensitized CoS2 composites is increased significantly due to the synergetic effect between the fullerene and the CoS2 nanoparticles

  7. Betulin and betulinic acid attenuate ethanol-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS), cytokine (TNF-α, TGF-β) production and by influencing intracellular signaling

    Background/aims: Liver fibrosis has been reported to be inhibited in vivo by oleanolic and ursolic acids. However, the mechanisms of the action of those triterpenoids are poorly understood. In this study, we aimed to determine the antifibrotic potential of other triterpenes, betulin and betulinic acid, and to characterize their influence on the signal transduction pathways involved in ethanol-activated hepatic stellate cells (HSCs). Methods: Investigated was the influence of preincubation of rat HSCs with betulin and betulinic acid, at non-toxic concentrations, on ethanol-induced toxicity, migration, and several markers of HSC activation such as smooth muscle α-actin (α-SMA) and procollagen I expression, release of reactive oxygen species (ROS) and cytokines: tumor necrosis factor-α (TNF-α) and tumor growth factor-β1 (TGF-β1), and production of metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2). To assess the mechanism of the action of those triterpenes, intracellular signals such as nuclear factor-κB (NFκB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) induced by ethanol were examined. Results: In vitro, betulin, but not betulinic acid, protected HSCs against ethanol toxicity. However, both betulin and betulinic acid inhibited the production of ROS by HSCs treated with ethanol and inhibited their migration as well as ethanol-induced TNF-α, and TGF-β1, production. Betulin and betulinic acid down-regulated ethanol-induced production of TIMP-1 and TIMP-2. Betulin and betulinic acid, also decreased ethanol-induced activity of MMP-2. In ethanol-induced HSCs, betulin inhibited the activation of the p38 MAPK and the JNK transduction pathways, while betulinic acid inhibited the JNK transduction pathway only. They also significantly inhibited phosphorylation of IκB and Smad 3 and attenuated the activation of TGF-β1 and NFκB/IκB transduction signaling. Conclusion: The results

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

    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

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

    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 pr...

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

    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 (O 2 - ) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O 2 - 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 chemiluminescen...

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

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

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-adminis...

  12. Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds

    Kowol, Christian R.; Heffeter, Petra; Miklos, Walter; Gille, Lars; Trondl, Robert; Cappellacci, Loredana; Berger, Walter; Keppler, Bernhard K.

    2011-01-01

    Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-amino-pyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone a...

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

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

    2016-06-01

    Reactive oxygen species (ROS) are continually generated as a consequence of the normal metabolism in aerobic organisms. Accumulation and release of ROS into cell take place in response to a wide variety of adverse environmental conditions including salt, temperature, cold stresses and pathogen attack, among others. In plants, peroxidases class III, NADPH oxidase (NOX) locates in cell wall and plasma membrane, respectively, may be mainly enzymatic systems involving ROS generation. It is well documented that ROS play a dual role into cells, acting as important signal transduction molecules and as toxic molecules with strong oxidant power, however some aspects related to its function during plant-pathogen interactions remain unclear. This review focuses on the principal enzymatic systems involving ROS generation addressing the role of ROS as signal molecules during plant-pathogen interactions. We described how the chloroplasts, mitochondria and peroxisomes perceive the external stimuli as pathogen invasion, and trigger resistance response using ROS as signal molecule. PMID:26950921

  14. Reactive oxygen species, ageing and the hormesis police.

    Ludovico, Paula; Burhans, William C

    2014-02-01

    For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis. PMID:23965186

  15. Reactive oxygen species in organ-specific autoimmunity.

    Di Dalmazi, Giulia; Hirshberg, Jason; Lyle, Daniel; Freij, Joudeh B; Caturegli, Patrizio

    2016-12-01

    Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response. PMID:27491295

  16. Mitochondrial reactive oxygen species modulate mosquito susceptibility to Plasmodium infection.

    Renata L S Gonçalves

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

  17. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

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

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. Conclusion We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection. PMID:22815925

  18. Reactive oxygen species are required for 5-HT-induced transactivation of neuronal platelet-derived growth factor and TrkB receptors, but not for ERK1/2 activation.

    Jeff S Kruk

    Full Text Available High concentrations of reactive oxygen species (ROS induce cellular damage, however at lower concentrations ROS act as intracellular second messengers. In this study, we demonstrate that serotonin (5-HT transactivates the platelet-derived growth factor (PDGF type β receptor as well as the TrkB receptor in neuronal cultures and SH-SY5Y cells, and that the transactivation of both receptors is ROS-dependent. Exogenous application of H₂O₂ induced the phosphorylation of these receptors in a dose-dependent fashion, similar to that observed with 5-HT. However the same concentrations of H₂O₂ failed to increase ERK1/2 phosphorylation. Yet, the NADPH oxidase inhibitors diphenyleneiodonium chloride and apocynin blocked both 5-HT-induced PDGFβ receptor phosphorylation and ERK1/2 phosphorylation. The increases in PDGFβ receptor and ERK1/2 phosphorylation were also dependent on protein kinase C activity, likely acting upstream of NADPH oxidase. Additionally, although the ROS scavenger N-acetyl-l-cysteine abrogated 5-HT-induced PDGFβ and TrkB receptor transactivation, it was unable to prevent 5-HT-induced ERK1/2 phosphorylation. Thus, the divergence point for 5-HT-induced receptor tyrosine kinase (RTK transactivation and ERK1/2 phosphorylation occurs at the level of NADPH oxidase in this system. The ability of 5-HT to induce the production of ROS resulting in transactivation of both PDGFβ and TrkB receptors may suggest that instead of a single GPCR to single RTK pathway, a less selective, more global RTK response to GPCR activation is occurring.

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

    van der Wijst, Monique

    2016-01-01

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

  20. Reactive oxygen species mediate growth and death in submerged plants

    Bianka eSteffens

    2013-06-01

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

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

    Monireh Mohsenzadegan

    2012-09-01

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

  2. Effects of MCI-186 upon neutrophil-derived active oxygens.

    Sumitomo, K; Shishido, N; Aizawa, H; Hasebe, N; Kikuchi, K; Nakamura, M

    2007-01-01

    Reactions of 3-methyl-1-phenyl-2-pyrazoline-5-one (MCI-186) with hypochlorous acid and superoxide were analysed by spectrophotometry and mass spectrometry. The results were applied to the neutrophil system to evaluate the scavenging activity of neutrophil-derived active oxygen species by MCI-186. MCI-186 reacted rapidly with hypochlorous acid (1 x 10(6) M(-1)s(-1)) to form a chlorinated intermediate, followed by a slow conversion to a new spectrum. MCI-186 consumed 3 moles of hypochlorous acid and did not react with superoxide. The newly synthesized fluorescence probes, 2-[6-(4'-amino)-phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (APF) and 2-[6-(4'-hydroxy)phenoxy-3H-anthen-3-on-9-yl]benzoic acid (HPF) successfully detected neutrophil-derived active oxygens (Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 2003; 278: 3170-3175). The rate constants for the reaction of hypochlorous acid with MCI-186 and fluorescence probes was in the order of MCI-186 > APF > HPF. Fluorescence due to the oxidation of APF and HPF was observed with the stimulated neutrophils. The result that the intensity from APF oxidation was higher than that from HPF oxidation is compatible with reports that APF selectively reacts with hypochlorous acid. Fluorescence due to oxidation of both APF and HPF decreased when the reactions were carried out in the presence of a fluorescence probe and MCI-186 in a dose-dependent manner. These results indicate that MCI-186 effectively scavenges neutrophil-derived hypochlorous acid and other active oxygens. PMID:17705989

  3. ROLES OF REACTIVE OXYGEN SPECIES IN THE SPERMATOGENESIS REGULATION

    GiuliaGUERRIERO

    2014-04-01

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

  4. Cross-talk between calcium and reactive oxygen species signaling

    Yuan YAN; Chao-liang WEI; Wan-rui ZHANG; He-ping CHENG; Jie LIU

    2006-01-01

    Calcium(Ca2+) and reactive oxygen species(ROS)constitute the most important intracellular signaling molecules participating in the regulation and integration of diverse cellular functions.Here we briefly review cross-talk between the two prominent signaling systems that finely tune the homeostasis and integrate functionality of Ca2+ and ROS in different types of cells.Ca2+ modulates ROS homeostasis by regulating ROS generation and annihilation mechanisms in both the mitochondria and the cytosol.Reciprocal redox regulation of Ca2+ homeostasis occurs in different physiological and pathological processes,by modulating components of the Ca2+ signaling toolkit and altering characteristics of local and global Ca2+ signals.Functionally,interactions between Ca2+ and ROS signaling systems can be both stimulatory and inhibitory,depending on the type of target proteins,the ROS species,the dose,duration of exposure,and the cell contexts.Such extensive and complex cross-talk might enhance signaling coordination and integration,whereas abnormalities in either system might propagate into the other system and undermine the stability of both systems.

  5. Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor ΚB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells

    Li J

    2014-03-01

    Full Text Available Jinchao Li,1,* Jun Li,2,* Ye Yue,1 Yiping Hu,1 Wenxiang Cheng,1 Ruoxi Liu,3 Xiaohua Pan,4 Peng Zhang1 1Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 2Emergency Surgery Department, Shaanxi Provincial People’s Hospital, Xi’an, 3Department of Orthopedics, Shandong University of Traditional Chinese Medicine, Jinan, 4Department of Orthopedics, Second Clinical Medical College, Jinan University, Shenzhen, People’ Republic of China *These authors contributed equally to this work Aims: Genistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA. However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression. Materials and methods: MH7A cells were stimulated with tumor necrosis factor (TNF-α and incubated with genistein, and interleukin (IL-1β, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF- ΚB was measured by a confocal fluorescence microscopy. The intracellular accumulation of reactive oxygen species (ROS was monitored using the fluorescent probe 5-6-chloromethyl-2´,7´-dichlorodihydrofluorescein diacetate. Signal-transduction protein expression was measured by Western blot. Results: Genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α -induced NF-ΚB translocation as well as phosphorylation of IΚB kinase-α/β and IΚBα, and also suppressed TNF-α-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might

  6. Photo-irradiation of proanthocyanidin as a new disinfection technique via reactive oxygen species formation.

    Keisuke Nakamura

    Full Text Available In the present study, the bactericidal effect of photo-irradiated proanthocyanidin was evaluated in relation to reactive oxygen species formation. Staphylococcus aureus suspended in proanthocyanidin aqueous solution was irradiated with light from a laser at 405 nm. The bactericidal effect of photo-irradiated proanthocyanidin depended on the concentration of proanthocyanidin, the laser irradiation time, and the laser output power. When proanthocyanidin was used at the concentration of 1 mg/mL, the laser irradiation of the bacterial suspension could kill the bacteria with a >5-log reduction of viable cell counts. By contrast, bactericidal effect was not observed when proanthocyanidin was not irradiated. In electron spin resonance analysis, reactive oxygen species, such as hydroxyl radicals, superoxide anion radicals, and hydrogen peroxide, were detected in the photo-irradiated proanthocyanidin aqueous solution. The yields of the reactive oxygen species also depended on the concentration of proanthocyanidin, the laser irradiation time, and the laser output power as is the case with the bactericidal assay. Thus, it is indicated that the bactericidal effect of photo-irradiated proanthocyanidin is exerted via the reactive oxygen species formation. The bactericidal effect as well as the yield of the oxygen radicals increased with the concentration of proanthocyanidin up to 4 mg/mL, and then decreased with the concentration. These findings suggest that the antioxidative activity of proanthocyanidin might prevail against the radical generation potency of photo-irradiated proanthocyanidin resulting in the decreased bactericidal effect when the concentration is over 4 mg/mL. The present study suggests that photo-irradiated proanthocyanidin whenever used in an optimal concentration range can be a new disinfection technique.

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

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

    2016-04-15

    It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner. PMID:26945820

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

    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

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

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

    2015-02-01

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

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

    Noah C. Jenkins

    2013-01-01

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

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

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

    2015-12-01

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

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

    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. Support nanostructure boosts oxygen transfer to catalytically active platinum nanoparticles

    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.

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

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

    2012-12-15

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

  15. Antifungal activity of some Cuban Zanthoxylum species.

    Diéguez-Hurtado, R; Garrido-Garrido, G; Prieto-González, S; Iznaga, Y; González, L; Molina-Torres, J; Curini, M; Epifano, F; Marcotullio, M C

    2003-06-01

    Ethanolic extracts of the trunk bark of Zanthoxylum fagara, Z. elephantiasis and Z. martinicense showed activity against different species of fungi. No antibacterial activity was detected. PMID:12781811

  16. Reactive Oxygen Species Alter Autocrine and Paracrine Signaling

    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.

  17. The connection of monocytes and reactive oxygen species in pain.

    Dagmar Hackel

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

  18. Are mitochondrial reactive oxygen species required for autophagy?

    Highlights: → Autophageal and apoptotic pathways were dissected in cytochrome c deficient cells. → Staurosporine (STS)-induced autophagy was not accompanied by ROS generation. → Autophagy was detectable in mitochondrial DNA deficient ρ0 cells. → Mitochondrial ROS are not required for the STS-induced autophagy in HeLa cells. -- Abstract: Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H2O2 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 ρo HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.

  19. Development of fluorometric reactive oxygen species assay for photosafety evaluation.

    Seto, Yoshiki; Ohtake, Hiroto; Kato, Masashi; Onoue, Satomi

    2016-08-01

    The present investigation involved an attempt to develop a new reactive oxygen species (ROS) assay system for the photosafety assessment of chemicals using 1,3-diphenylisobenzofuran (DPBF), a fluorescent probe for monitoring ROS generation. The assay conditions of the fluorometric ROS (fROS) assay were optimized focusing on the solvent system, concentration of DPBF, fluorescent determination, screening run time and reproducibility. The photoreactivity of 21 phototoxic and 11 non-phototoxic compounds was assessed by fROS assay, and the obtained ROS data were compared with the results from a micellar ROS (mROS) assay and in vitro/in vivo phototoxicity information to confirm the predictive capacity of the fROS assay. In the optimized fROS assay, intra-day and inter-day precision levels (coefficient of variation) were found to be below 5%, and the Z'-factor for DPBF fluorescence quenching showed a large separation between positive and negative controls. Of all tested compounds, 3 false positive and 7 false negative predictions were observed in the fROS assay, and the negative predictivity for the fROS assay was found to be lower than that for the mROS assay. Although the fROS assay has some limitations, the procedures for it were highly simplified with a marked reduction in screening run time and one analytical sample for monitoring ROS generation from compounds. The fROS assay has the potential to become a new tool for photosafety assessment at an early stage of product development. PMID:27058001

  20. Are mitochondrial reactive oxygen species required for autophagy?

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

    2011-08-19

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

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

    Rachel McCormick

    2016-08-01

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

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

    Gérard Jean-Louis

    2010-07-01

    Full Text Available Abstract Background Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. Methods We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz. After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyltheophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation between the groups by a variance analysis and post hoc test. Results Desflurane 6% (84 ± 6% of baseline enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P N-mercaptopropionylglycine (54 ± 3% of baseline, 8-(p-Sulfophenyltheophylline (62 ± 9% of baseline, HOE140 (58 ± 6% of baseline abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline and bradykinin (83 ± 4% of baseline induced postconditioning (P vs control, N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively. Conclusions In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin

  3. Reactive Oxygen Species Derived from NOX3 and NOX5 Drive Differentiation of Human Oligodendrocytes

    Accetta, Roberta; Damiano, Simona; Morano, Annalisa; Mondola, Paolo; Paternò, Roberto; Avvedimento, Enrico V.; Santillo, Mariarosaria

    2016-01-01

    Reactive oxygen species (ROS) are signaling molecules that mediate stress response, apoptosis, DNA damage, gene expression and differentiation. We report here that differentiation of oligodendrocytes (OLs), the myelin forming cells in the CNS, is driven by ROS. To dissect the OL differentiation pathway, we used the cell line MO3-13, which display the molecular and cellular features of OL precursors. These cells exposed 1–4 days to low levels of H2O2 or to the protein kinase C (PKC) activator,...

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

    Khan, Saeed R

    2014-09-01

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

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

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

    2012-10-01

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

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

    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.

  7. Angiotensin II-Induced Production of Mitochondrial Reactive Oxygen Species: Potential Mechanisms and Relevance for Cardiovascular Disease

    Dikalov, Sergey I.; Nazarewicz, Rafal R.

    2013-01-01

    Significance: The role of reactive oxygen species (ROS) in angiotensin II (AngII) induced endothelial dysfunction, cardiovascular and renal remodeling, inflammation, and fibrosis has been well documented. The molecular mechanisms of AngII pathophysiological activity involve the stimulation of NADPH oxidases, which produce superoxide and hydrogen peroxide. AngII also increases the production of mitochondrial ROS, while the inhibition of AngII improves mitochondrial function; however, the speci...

  8. Radiation induces aerobic glycolysis through reactive oxygen species

    Background and purpose: Although radiation induced reoxygenation has been thought to increase radiosensitivity, we have shown that its associated oxidative stress can have radioprotective effects, including stabilization of the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to promote treatment resistance. Thus, we hypothesized that reoxygenation after radiation would increase glycolysis. We previously showed that blockade of oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation can downregulate HIF-1 activity. Here we tested whether concurrent use of this drug with radiotherapy would reduce the switch to a glycolytic phenotype. Materials and methods: 40 mice with skin fold window chambers implanted with 4T1 mammary carcinomas were randomized into (1) no treatment, (2) radiation alone, (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were imaged on the ninth day following tumor implantation (30 h following radiation treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was measured by using hyperspectral imaging to quantify oxygenation state. Results: Mice treated with radiation showed significantly higher 2-NBDG fluorescence compared to controls (p = 0.007). Hemoglobin saturation analysis demonstrated reoxygenation following radiation, coinciding with the observed increase in glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a significant reduction in 2-NBDG fluorescence compared to effects seen after radiation alone, while having no effect on reoxygenation. Conclusions: Radiation induces an increase in tumor glucose demand approximately 30 h following therapy during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic glycolysis when used

  9. Activation of Reactive Oxygen Species and Defense Responses in Tobacco Cells Treated with Riboflavin%核黄素对烟草悬浮细胞活性氧和防卫反应的激活作用

    刘菲; 魏芳芳; 王蕾; 刘辉; 梁元存; 刘爱新

    2009-01-01

    [Objective] To study the triggering defense responses in tobacco suspension cells after treated with riboflavin,reactive oxygen species (ROS) and defense-related responses were investigated together with their related effects involving in calcium signals and protein kinases.[method]tobacco suspension cells were treated 1 mmol·L~(-1) riboflavin or pretreated with inhibitors including calcium surrogate La~(3+),calcium chelator EGTA and staurosporine which is an inhibitor of serine/threonine protein kinase.A series of dynamic defense responses were then studied with several methods,including semiquantitative RT-PCR (reverse transcriptase-polymerase chain reaction) and HPLC (high performance liquid chromatography) techniques.[Result] It was identified that a series of defense-related responses were induced in tobacco suspension cells after treated with riboflavin,such as an oxidative burst,resulting in alkalization of the extracellular medium,activated the expression of four defense-related genes,and the scopoletin accumulation.And all the tested three inhibitors were shown in suppressing the riboflavin triggered defense responses at difference levels.[Conclusion]These results suggest that riboflavin triggers plant basal defense signal pathway which are also concerned with calcium signal pathway and protein phosphorylation in tobacco cell suspensions as an elicitor.%[目的]研究核黄素处理烟草悬浮细胞后,激活的氧进发和防卫反应,以及钙信号和蛋白激酶对这些事件的影响.[方法]1mmol·L~(-1)核黄素处理烟草悬浮细胞,用半定量RT-PCR(reverse transcriptase-polymerase chain reaction)和高效液相色谱(high performance liquid chromatography,HPLC)等方法测定一系列防卫反应,并用钙离子通道抑制剂LaCl3、钙离子螯合剂EGTA和一种丝氨酸/苏氨酸蛋白激酶抑制剂staurosporine处理细胞,测定防卫反应的变化.[结果]1mmol·L~(-1)核黄素处理悬浮细胞后,产生了氧进发、导致培

  10. Henry's Law Activity of Oxygen in Molten Iron

    Matousek, J. W.

    2015-09-01

    A model is proposed for the solubility of oxygen in molten iron in dilute solutions in which the oxygen exists in two states, free and associated. Only the free oxygen has thermodynamic activity in the sense of interaction with an electrochemical cell to produce the voltage described by the Nernst equation.

  11. Evaluation of the Catalytic Activity and Cytotoxicity of Palladium Nanocubes. The Role of Oxygen

    Dahal, Eshan; Curtiss, Jessica; Subedi, Deepak; Chen, Gen; Houston, Jessica P.; Smirnov, Sergei

    2015-01-01

    Recently it has been reported that palladium nanocubes (PdNC) are capable of generating singlet oxygen without photo-excitation simply via chemisorption of molecular oxygen on its surface. Such a trait would make PdNC a highly versatile catalyst suitable in organic synthesis and a Reactive Oxygen Species (ROS) inducing cancer treatment reagent. Here we thoroughly investigated the catalytic activity of PdNC with respect to their ability to produce singlet oxygen and to oxidize 3,5,3′,5′-tetram...

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

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

    2002-05-31

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

  13. Active oxygen involvement in developmental processes in Populus

    Srivastava, Vaibhav

    2009-01-01

    In plants, oxidative stress is result of disruption of the cellular redox metabolism and is caused by a variety of stress conditions (abiotic and/or biotic). This leads to the induction of several mechanisms that protect against disruption of the redox balance, as well as mechanisms to assist in recovery from toxicity/damage caused by increased cellular levels of reactive oxygen species (ROS). The superoxide dismutase enzymes (SODs) are key component of the reactive oxygen species gene networ...

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

    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.

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

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

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

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

    2015-10-01

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

  17. Solubility and activity of oxygen in liquid scandium

    On the basis of available data on oxygen solubility in iron group metals the energy characteristics and the dependence of metal/oxygen change energies on a metal ordinal number are obtained to predict unknown values for manganese, chromium, vanadium, titanium and scandium using the extrapolation method. The testing for manganese shows a good agreement between experiments and calculation. A similar technique is applied to obtain the data on scandium/oxygen exchange energy, oxygen activity and solubility in liquid scandium

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

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

    2010-01-01

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

  19. Reactive oxygen species in melanoma and its therapeutic implications.

    Wittgen, H.G.; Kempen, L.C. van

    2007-01-01

    Oxidative phosphorylation in the mitochondria is an important energy-producing process for eukaryotic cells, but this process can also result in producing potentially cell-damaging side products. Oxygen is the final proton acceptor in this cascade of electron/proton transfer and results in harmless

  20. 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

    Hseu, You-Cheng [Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan (China); Department of Molecular and Cellular Oncology, University of Texas, MD Anderson Cancer Center, TX 77030 (United States); Senthil Kumar, K.J. [Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan (China); Chen, Chih-Sheng; Cho, Hsin-Ju; Lin, Shu-Wei; Shen, Pei-Chun [Institute of Nutrition, China Medical University, Taichung 40402, Taiwan (China); Lin, Cheng-Wen [Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan (China); Lu, Fung-Jou [Institute of Medicine, Chun Shan Medical University, Taichung 40201, Taiwan (China); Yang, Hsin-Ling, E-mail: hlyang@mail.cmu.edu.tw [Institute of Nutrition, China Medical University, Taichung 40402, Taiwan (China); Department of Molecular and Cellular Oncology, University of Texas, MD Anderson Cancer Center, TX 77030 (United States)

    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

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

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

  2. Transient species produced in irradiated alkaline aqueous solutions containing oxygen

    The spectra and decay kinetics of the optical absorption in the UV region and at 430nm (maximum of the ozonide ion absorption), were investigated in oxygenated neutral, slightly and strongly alkaline aqueous solutions. It is assumed that the initial absorption after the pulse in oxygenated alkaline solutions is due to the ozonide ion O3-, superoxide radical ion O2- and ozone O3. The long-living absorption in these solutions cannot be excluded as to be probably caused by the ozone O3 or some product formed from O2- or an alkaline stabilized form of this radical-ion. The advantage of applying additional non-optical measurements of the system is shown on the example of H2O2 role played in the mechanism. (author)

  3. Roles of Reactive Oxygen and Nitrogen Species in Pain

    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 s...

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

    Allertz, Carl; Selleby, Malin; Sichen, Du

    2016-06-01

    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.

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

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

    2011-08-01

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

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

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

    2015-08-01

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

  7. Antimicrobial Activity of Some Trigonella Species

    Rakhee Shyam Dangi; Dasharath Oulkar; Prashant Dhakephalkar; Sanjay Kumar Singh; Kaushik Banerjee; Dattatray Naik; Shubhada Tamhankar; Suryaprakasa Rao

    2016-01-01

    The genus Trigonella includes many medicinal and aromatic plant species used in traditional as well as veterinary medicines for different diseases, alone or in combination with other remedies. The crude methanol extracts of 15 Trigonella species were assayed for antimicrobial activity against four medicinally important multidrug resistant clinical isolates, five plant pathogenic bacteria and five fungi.Three species showed a broad spectrum of antibacterial activity inhibiting all the test bac...

  8. Stannous chloride mediates single strand breaks in plasmid DNA through reactive oxygen species formation

    Full text. Stannous ion (Sn) has been employed in many activities related to human beings, as in nuclear medicine, or in food industry. The effect of Sn on supercoiled plasmid DNA was studied by the alteration of plasmid topology in neutral and acidic pH by gel electrophoresis; the transformation efficiency of a wild type Escherichia coli (E. coli) strain; and the patterns of electrophoretic mobility with the digested plasmid. Exposure of plasmid 9.1 DNA to Sn ion caused DNA single-strand breaks (ssb), revealed by agarose gel electrophoresis as an increase in the proportion of the open circular form at the expense of the supercoiled form. Addition of hydroxyl (OH) scavenger (sodium benzoate, 100 mM) inhibited the DNA damage (58%) showing the involvement of such reactive oxygen species (R O S) like -OH Decrease of transformation efficiency and alteration in the patterns of electrophoretic mobility with the digested plasmid is also observed. Our results are consistent with a mechanism involving the generation of reactive oxygen species, such as -OH by a Fenton-like reaction, and also a complexation of stannous ions to DNA, that could explain the decrease of its electrophoretic mobility and protection effect exerted during Sn Cl2 treatment at acidic pH

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

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

    2009-08-01

    Infection with ectomycorrhizal fungi can increase the ability of plants to resist drought stress through morphophysiological and biochemical mechanisms. However, the metabolism of antioxidative enzyme activities in the ectomycorrhizal symbiosis remains poorly understood. This study investigated biomass production, reactive oxygen metabolism (hydrogen peroxide and malondialdehyde concentration) and antioxidant enzyme activity (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) in pure cultures of the ectomycorrhizal fungi Descolea antartica Sing. and Pisolithus tinctorius (Pers.) Coker & Couch, and non-mycorrhizal and mycorrhizal roots of Nothofagus dombeyi (Mirb.) roots under well-watered conditions and drought conditions (DC). The studied ectomycorrhizal fungi regulated their antioxidative enzyme metabolism differentially in response to drought, resulting in cellular damage in D. antartica but not in P. tinctorius. Ectomycorrhizal inoculation and water treatment had a significant effect on all parameters studied, including relative water content of the plant. As such, N. dombeyi plants in symbiosis experienced a lower oxidative stress effect than non-mycorrhizal plants under DC. Additionally, ectomycorrhizal N. dombeyi roots showed a greater antioxidant enzyme activity relative to non-mycorrhizal roots, an effect which was further expressed under DC. The association between the non-specific P. tinctorius and N. dombeyi had a more effective reactive oxygen species (ROS) metabolism than the specific D. antartica-N. dombeyi symbiosis. We conclude that the combination of effective ROS prevention and ROS detoxification by ectomycorrhizal plants resulted in reduced cellular damage and increased plant growth relative to non-mycorrhizal plants under drought. PMID:19483186

  10. Adaptive alterations in the activities of scavengers of active oxygen in cucumber cotyledons irradiated with UV-B

    UV-B (290–320 nm) irradiation considerably reduced the cotyledon size of cucumber (Cucumis sativus L.) seedlings at 20 °C, and the extent of growth inhibition was reduced at 25 °C. At both temperatures, levels of endogenous scavengers and activities of active oxygen-scavenging enzymes were affected by UV-B irradiation. In particular, ascorbate peroxidase activity increased considerably, suggesting that active oxygen species might participate in the growth inhibition induced by UV-B irradiation. However, since no positive correlation was detected between the dependence of growth inhibition on temperature and the capacity to scavenge active species of oxygen, other mechanisms must be involved in the changes in the responses to UV-B that are related to temperature

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

    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 (H2O2) 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

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

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

    2014-11-01

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

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

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

    2015-05-15

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

  14. Photocatalytic Reactive Oxygen Species Formation by Semiconductor-Metal Hybrid Nanoparticles. Toward Light-Induced Modulation of Biological Processes.

    Waiskopf, Nir; Ben-Shahar, Yuval; Galchenko, Michael; Carmel, Inbal; Moshitzky, Gilli; Soreq, Hermona; Banin, Uri

    2016-07-13

    Semiconductor-metal hybrid nanoparticles manifest efficient light-induced spatial charge separation at the semiconductor-metal interface, as demonstrated by their use for hydrogen generation via water splitting. Here, we pioneer a study of their functionality as efficient photocatalysts for the formation of reactive oxygen species. We observed enhanced photocatalytic activity forming hydrogen peroxide, superoxide, and hydroxyl radicals upon light excitation, which was significantly larger than that of the semiconductor nanocrystals, attributed to the charge separation and the catalytic function of the metal tip. We used this photocatalytic functionality for modulating the enzymatic activity of horseradish peroxidase as a model system, demonstrating the potential use of hybrid nanoparticles as active agents for controlling biological processes through illumination. The capability to produce reactive oxygen species by illumination on-demand enhances the available peroxidase-based tools for research and opens the path for studying biological processes at high spatiotemporal resolution, laying the foundation for developing novel therapeutic approaches. PMID:27224678

  15. Virion disruption by ozone-mediated reactive oxygen species.

    Murray, Byron K; Ohmine, Seiga; Tomer, David P; Jensen, Kendal J; Johnson, F Brent; Kirsi, Jorma J; Robison, Richard A; O'Neill, Kim L

    2008-10-01

    It is well documented in the scientific literature that ozone-oxygen mixtures inactivate microorganisms including bacteria, fungi and viruses (Hoff, J.C., 1986. Inactivation of microbial agents by chemical disinfectants. EPA 600 S2-86 067. Office of Water, U.S. Environmental Protection Agency, Washington, DC; Khadre, M.A., Yousef, A.E., Kim, J.-G., 2001. Microbiological aspects of ozone applications in food: a review. J. Food Sci. 66, 1242-1252). In the current study, delivery and absorption of precisely known concentrations of ozone (in liquid media) were used to inactivate virus infectivity. An ozone-oxygen delivery system capable of monitoring and recording ozone concentrations in real time was used to inactivate a series of enveloped and non-enveloped viruses including herpes simplex virus type-1 (HHV-1, strain McIntyre), vesicular stomatitis Indiana virus (VSIV), vaccinia virus (VACV, strain Elstree), adenovirus type-2 (HAdV-2), and the PR8 strain of influenza A virus (FLUAVA/PR/8/34/H1N1; FLUAV). The results of the study showed that ozone exposure reduced viral infectivity by lipid peroxidation and subsequent lipid envelope and protein shell damage. These data suggest that a wide range of virus types can be inactivated in an environment of known ozone exposure. PMID:18598719

  16. A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model.

    Bruni, Antonio; Pepper, Andrew R; Gala-Lopez, Boris; Pawlick, Rena; Abualhassan, Nasser; Crapo, James D; Piganelli, Jon D; Shapiro, A M James

    2016-07-01

    Islet transplantation is a highly effective treatment for stabilizing glycemic control for select patients with type-1 diabetes. Despite improvements to clinical transplantation, single-donor transplant success has been hard to achieve routinely, necessitating increasing demands on viable organ availability. Donation after circulatory death (DCD) may be an alternative option to increase organ availability however, these organs tend to be more compromised. The use of metalloporphyrin anti-inflammatory and antioxidant (MnP) compounds previously demonstrated improved in vivo islet function in preclinical islet transplantation. However, the administration of MnP (BMX-001) in a DCD islet isolation and transplantation model has yet to be established. In this study, murine donors were subjected to a 15-min warm ischemic (WI) period prior to isolation and culture with or without MnP. Subsequent to one-hour culture, islets were assessed for in vitro viability and in vivo function. A 15-minute WI period significantly reduced islet yield, regardless of MnP-treatment relative to yields from standard isolation. MnP-treated islets did not improve islet viability compared to DCD islets alone. MnP-treatment did significantly reduce the presence of extracellular reactive oxygen species (ROS) (p < 0 .05). Marginal, syngeneic islets (200 islets) transplanted under the renal capsule exhibited similar in vivo outcomes regardless of WI or MnP-treatment. DCD islet grafts harvested 7 d post-transplant exhibited sustained TNF-α and IL-10, while MnP-treated islet-bearing grafts demonstrated reduced IL-10 levels. Taken together, 15-minute WI in murine islet isolation significantly impairs islet yield. DCD islets do indeed demonstrate in vivo function, though MnP therapy was unable to improve viability and engraftment outcomes. PMID:27220256

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

    Keiichi Matsubara

    2015-03-01

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

  18. Texas Endangered Species Activity Book.

    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.…

  19. PGC-1α and reactive oxygen species regulate human embryonic stem cell-derived cardiomyocyte function.

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

    2013-01-01

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

  20. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds.

    Boldyrev, Alexander; Bulygina, Elena; Leinsoo, Toomas; Petrushanko, Irina; Tsubone, Shiori; Abe, Hiroki

    2004-01-01

    Carnosine and related compounds were compared in terms of their abilities to decrease the levels of reactive oxygen species (ROS) in suspensions of isolated neurons activated by N-methyl-D-aspartic acid (NMDA) using both stationary fluorescence measurements and flow cytometry. Carnosine was found to suppress the fluorescent signal induced by ROS production and decreased the proportion of highly fluorescent neurons, while histidine showed opposite effects. N-Acetylated derivatives of both carnosine and histidine demonstrated weak (statistically indistinguishable) suppressive effects on the ROS signal. N-Methylated derivatives of carnosine suppressed intracellular ROS generation to the same extent as carnosine. This rank of effectiveness is distinct from that previously obtained for the anti-radical ability of CRCs (anserine>carnosine>ophidine). These differences suggest that the similar ability of carnosine and its N-methylated derivatives to protect neuronal cells against the excitotoxic effect of NMDA is not solely related to the antioxidant properties of these compounds. PMID:14698913

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

    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.

  2. Induction of caspase 8 and reactive oxygen species by ruthenium-derived anticancer compounds with improved water solubility and cytotoxicity.

    Vidimar, Vania; Meng, Xiangjun; Klajner, Marcelina; Licona, Cynthia; Fetzer, Ludivine; Harlepp, Sébastien; Hébraud, Pascal; Sidhoum, Marjorie; Sirlin, Claude; Loeffler, Jean-Philippe; Mellitzer, Georg; Sava, Gianni; Pfeffer, Michel; Gaiddon, Christian

    2012-12-01

    Organometallic compounds which contain metals, such as ruthenium or gold, have been investigated as a replacement for platinum-derived anticancer drugs. They often show good antitumor effects, but the identification of their precise mode of action or their pharmacological optimization is still challenging. We have previously described a class of ruthenium(II) compounds with interesting anticancer properties. In comparison to cisplatin, these molecules have lower side effects, a reduced ability to interact with DNA, and they induce cell death in absence of p53 through CHOP/DDIT3. We have now optimized these molecules by improving their cytotoxicity and their water solubility. In this article, we demonstrate that by changing the ligands around the ruthenium we modify the ability of the compounds to interact with DNA. We show that these optimized molecules reduce tumor growth in different mouse models and retain their ability to induce CHOP/DDIT3. However, they are more potent inducers of cancer cell death and trigger the production of reactive oxygen species and the activation of caspase 8. More importantly, we show that blocking reactive oxygen species production or caspase 8 activity reduces significantly the activity of the compounds. Altogether our data suggest that water-soluble ruthenium(II)-derived compounds represent an interesting class of molecules that, depending on their structures, can target several pro-apoptotic signaling pathways leading to reactive oxygen species production and caspase 8 activation. PMID:22964219

  3. Reactive species formed on proteins exposed to singlet oxygen

    Davies, Michael Jonathan

    2004-01-01

    hydroperoxides, which can be reduced to the corresponding alcohols; other products arising from radical intermediates can also be generated, particularly in the presence of UV light and metal ions. With His side-chains, poorly characterised peroxides are also formed. Reaction with Met and Cys has been proposed...... molecular oxidation of thiol residues an important reaction. This can result in the inactivation of cellular enzymes and the oxidation of other biological targets. Protein cross-linking and aggregation can also be induced by reactive species formed on photo-oxidised proteins, though the nature of the...

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

    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.

  5. Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice.

    Nan Liu

    Full Text Available BACKGROUNDS: Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP mediated immune response, the role of reactive oxygen species (ROS in brain-skin-axis regulation system remains unknown. OBJECTIVES: The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress which induced abnormal of hair cycle. METHODS AND RESULTS: Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px in CRS mice skin. In addition, SP receptor antagonist (RP67580 reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger also restored hair cycle, reduced SP protein expression and mast cell activation. CONCLUSIONS: Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.

  6. Accumulation of non-superoxide anion reactive oxygen species mediates nitrogen-limited alcoholic fermentation by Saccharomyces cerevisiae

    Ferreira, Ana Mendes; Marques, Belém Sampaio; Barbosa, Catarina; Rodrigues, Fernando José dos Santos; Costa, Vitor; Faia, A. Mendes; Ludovico, Paula; Leão, Cecília

    2010-01-01

    Throughout alcoholic fermentation, nitrogen depletion is one of the most important environmental stresses that can negatively affect the yeast metabolic activity and ultimately leads to fermentation arrest. Thus, the identification of the underlying effects and biomarkers of nitrogen limitation is valuable for controlling, and therefore optimizing, alcoholic fermentation. In this study, reactive oxygen species (ROS), plasma membrane integrity, and cell cycle were evaluated in a wine strain of...

  7. Reactive oxygen and nitrogen (ROS and RNS) species generation and cell death in tomato suspension cultures—Botrytis cinerea interaction

    Pietrowska, E.; Różalska, S.; Kaźmierczak, A.; Nawrocka, J.; Małolepsza, U.

    2014-01-01

    This article reports events connected to cell survival and Botrytis cinerea infection development in cell suspension cultures of two tomato cultivars which show different levels of susceptibility to the pathogen: cv. Corindo (more susceptible) and cv. Perkoz (less susceptible). In parallel changes in reactive oxygen (ROS) and nitrogen (RNS) species generation and in S-nitrosoglutathione reductase (GSNOR) activity were studied. In vivo staining methods with acridine orange (AO) and ethidium br...

  8. Involvement of reactive oxygen species during early stages of ectomycorrhiza establishment between Castanea sativa and Pisolithus tinctorius

    Baptista, Paula; Martins, Anabela; Pais, M.S.; Tavares, Rui Manuel; Lino-Neto, Teresa

    2007-01-01

    Evidence for the participation of reactive oxygen species (ROS) and antioxidant systems in ectomycorrhizal(ECM) establishment is lacking. In this paper, we evaluated ROS production and the activities of superoxide dismutase (SOD) and catalase (CAT) during the early contact of the ECM fungus Pisolithus tinctorius with the roots of Castanea sativa (chestnut tree). Roots were placed in contact with P. tinctorius mycelia, and ROS production was evaluated by determining the level...

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

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

    2015-09-01

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

  10. Antimicrobial Activity of Some Trigonella Species

    Rakhee Shyam Dangi

    2016-03-01

    Full Text Available The genus Trigonella includes many medicinal and aromatic plant species used in traditional as well as veterinary medicines for different diseases, alone or in combination with other remedies. The crude methanol extracts of 15 Trigonella species were assayed for antimicrobial activity against four medicinally important multidrug resistant clinical isolates, five plant pathogenic bacteria and five fungi.Three species showed a broad spectrum of antibacterial activity inhibiting all the test bacteria. Acidified ethanolic extract of the most promising species, T. suavissima was purified by column chromatography. Characterization of a partially purified ethyl acetate fraction by LC/ESI/MS showed the presence of 7’4’ dihydroxy flavone and (2E-3-{5-[4-(Ethoxycarbonylphenyl]furan-2-yl}prop-2-enoate Three species showed strong antifungal activity against Aspergillus niger and Fusarium solani. The saponin extract of T. spicata showed a selective activity against A. niger and the sapogenin extract against F. solani. A polyhydroxylated alkaloid was isolated from the sapogenin extract of T. spicata using chromatographic techniques with structural characterization done by LC/ESI/MS, 13C and 1H NMR. The study reveals that Trigonella species are potential sources of natural compounds that may act as antimicrobial agents. It represents the most extensive survey of antimicrobial activity in Trigonella done to date.