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Sample records for active oxygen species

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

    Science.gov (United States)

    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.

    Science.gov (United States)

    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

    Lifescience Database Archive (English)

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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Reactive oxygen species in signalling the transcriptional activation of WIPK expression in tobacco.

    Science.gov (United States)

    Xu, Juan; Yang, Kwang-Yeol; Yoo, Seung Jin; Liu, Yidong; Ren, Dongtao; Zhang, Shuqun

    2014-07-01

    Plant mitogen-activated protein kinases represented by tobacco WIPK (wounding-induced protein kinase) and its orthologs in other species are unique in their regulation at transcriptional level in response to stress and pathogen infection. We previously demonstrated that transcriptional activation of WIPK is essential for induced WIPK activity, and activation of salicylic acid-induced protein kinase (SIPK) by the constitutively active NtMEK2(DD) is sufficient to induce WIPK gene expression. Here, we report that the effect of SIPK on WIPK gene expression is mediated by reactive oxygen species (ROS). Using a combination of pharmacological and gain-of-function transgenic approaches, we studied the relationship among SIPK activation, WIPK gene activation in response to fungal cryptogein, light-dependent ROS generation in chloroplasts, and ROS generated via NADPH oxidase. In the conditional gain-of-function GVG-NtMEK2(DD) transgenic tobacco, induction of WIPK expression is dependent on the ROS generation in chloroplasts. Consistently, methyl viologen, an inducer of ROS generation in chloroplasts, highly activated WIPK expression. In addition to chloroplast-originated ROS, H(2)O(2) generated from the cell-surface NADPH oxidase could also activate WIPK gene expression, and inhibition of cryptogein-induced ROS generation also abolished WIPK gene activation. Our data demonstrate that WIPK gene activation is mediated by ROS, which provides a mechanism by which ROS influence cellular signalling processes in plant stress/defence response.

  6. Reactive oxygen species activity in the interaction of rice with Erwinia chrysanthemi pv. zeae

    Institute of Scientific and Technical Information of China (English)

    Qiongguang LIU; Landi HE; Jingyi ZHANG; Yutao WANG; Zhenzhong WANG

    2008-01-01

    Activities of reactive oxygen species (ROS) were investigated in the interaction between rice and Erwinia chrysanthemi pv. zeae. Results showed that variety (128) had higher increases in activity compared to those in the susceptible variety (Texian 13) 24 hours after bacteria inoculation. The activities of superoxide dismutase (SOD) increased in 128 and Texian 13 twenty-four hours after inoculation and then decreased, but the SOD activity in 128 was found to be usually lower than that in Texian 13. The CAT activity in Texian 13 had two peaks at 24 h and 96 h after inoculation, while little change was seen in 128. In conclusion, ROS and its related enzymes could be correlated to rice resistance against E. chrysanthemi pv. zeae.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  10. In vitro antifilarial activity of Azadirachta indica aqueous extract through reactive oxygen species enhancement

    Institute of Scientific and Technical Information of China (English)

    Niladri Mukherjee; Prasanta Saini; Suprabhat Mukherjee; Priya Roy; Santi P. Sinha Babu

    2014-01-01

    Objective:To evaluate an aqueous preparation from the Azadirachta indica leaves (AEA) against Setaria cervi (S. cervi), a model filarial parasite. Methods:In vitro efficacy of AEA was evaluated against S. cervi through estimation of relative motility value, dye exclusion test and MTT assay. Visible morphological alterations were monitored using conventional microscopic techniques in microfilariae and haematoxylin-eosin stained sections of AEA-treated adults. Results:Enhancement of reactive oxygen species in S. cervi treated with AEA was established through alteration in the activity of glutathione S-transferase, superoxide dismutase, catalase, peroxidase and level of superoxide anion and reduced glutathione. Conclusions:In vitro filaricidal activity of AEA is possibly through disturbing redox homeostasis by down-regulating and altering the level of some key antioxidants and regulatory enzymes like reduced glutathione, glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase of S. cervi.

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

    Science.gov (United States)

    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.

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

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    Trejo-Solís Cristina

    2012-04-01

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

  13. Reactive oxygen species scavenging activity of aminoderivatized chitosan with different degree of deacetylation.

    Science.gov (United States)

    Je, Jae-Young; Kim, Se-Kwon

    2006-09-01

    Chitosans with different degree of deacetylation were prepared from crab shell chitin in the presence of alkali. Aminoderivatized chitosan derivatives were prepared in addition of amino functional groups at a hydroxyl site in the chitosan backbone. Six kinds of aminoderivatized chitosan such as aminoethyl-chitosan (AEC90), dimethylaminoethyl-chitosan (DMAEC90), and diethylaminoethyl-chitosan (DEAEC90), which were prepared from 90% deacetylated chitosan, and AEC50, DMAEC50 and DEAEC50, which were prepared from 50% deacetylated chitosan, were prepared and their reactive oxygen species (ROS) scavenging activities were investigated against hydroxyl radical, superoxide anion radical and hydrogen peroxide. The electron spin resonance (ESR) spectrum revealed that AEC90 showed the highest scavenging effects against hydroxyl and superoxide anion radical, the effects were 91.67% and 65.34% at 0.25 and 5 mg/mL, respectively. For hydrogen peroxide scavenging effect, DEAEC90 exhibited the strongest activity. These results suggest that the scavenging effect depends on their degree of deacetylation and substituted group.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Wang, Yan; Zhang, Beilei; Liu, Wei; Dai, Yunpeng; Shi, Yaru; Zeng, Qi; Wang, Fu

    2016-04-19

    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.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

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    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.

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

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    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2016-08-01

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

  3. The interaction of copper (Cu++) with the erythrocyte membrane and 2,3-dimercaptopropanesulphonate in vitro: a source of activated oxygen species.

    Science.gov (United States)

    Aaseth, J; Ribarov, S; Bochev, P

    1987-10-01

    The therapy of copper poisoning and of Wilson's disease with 2,3-dimercaptopropane-1-sulphonate (DMPS) may increase the copper-induced haemolysis. Some aspects of the mechanism of this effect were investigated. The possible generation of activated oxygen species during the interaction of Cu++ and DMPS was studied using a chemiluminescent method detecting oxygen radicals. It was found that incubation of DMPS with copper ions (free or bond with erythrocyte membranes) is accompanied with generation of oxygen radicals. Activated oxygen species produced via O2- are able to increase the haemolytic effects of cupric salts. Hence DMPS treatment in cases of copper poisonings or Wilson's disease may involve risk of side effects on the basis of activated oxygen species generation.

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

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    Andrzej Borkowski

    2016-09-01

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

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

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    Haohao Wu

    2014-03-01

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

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

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    Massimo Malerba

    2015-01-01

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

  7. Reactive oxygen and nitrogen species in defense/stress responses activated by chitosan in sycamore cultured cells.

    Science.gov (United States)

    Malerba, Massimo; Cerana, Raffaella

    2015-01-29

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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

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

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    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.

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

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    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.

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

    Science.gov (United States)

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

    2009-02-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species.

    Science.gov (United States)

    Ren, Jian-Dong; Wu, Xiao-Bo; Jiang, Rui; Hao, Da-Peng; Liu, Yi

    2016-01-01

    The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1β, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubiquitination, a non-transcriptional priming signal of NLRP3 in response to the stimulation of LPS. Additionally, the removal of mtROS by H2 reduced the generation of oxidized mitochondrial DNA and consequently decreased its binding to NLRP3, thereby inhibiting the NLRP3 inflammasome activation. Our findings have, for the first time, revealed the novel mechanism underlying the inhibitory effect of molecular hydrogen on LPS-caused NLRP3 inflammasome activation, highlighting the promising application of this new antioxidant in the treatment of LPS-associated inflammatory pathological damage.

  1. Antioxidant enzyme activity in bacterial resistance to nicotine toxicity by reactive oxygen species.

    Science.gov (United States)

    Shao, Tiejuan; Yuan, Haiping; Yan, Bo; Lü, Zhenmei; Min, Hang

    2009-10-01

    We analyzed superoxide dismutase (SOD), catalase (CAT), and ATPase activities in the highly nicotine-degrading strain Pseudomonas sp. HF-1 and two standard strains Escherichia coli and Bacillus subtilis in an attempt to understand antioxidant enzymes in bacteria are produced in response to nicotine, which increases the virulence of the bacteria. Nicotine had different effects on different antioxidant enzymes of different bacteria. SOD plays a more important role in resistance to nicotine stress in E. coli than it does in CAT. Multiple antioxidant enzymes are involved in combating oxidative stress caused by nicotine in Pseudomonas sp. HF-1. The contribution of a particular antioxidant enzyme for protection from nicotine stress varies with the growth phase involved. The inhibition of ATPase in Pseudomonas sp. HF-1 at the stationary phase was enhanced with increasing nicotine concentration, showing a striking dose-response relationship. Nicotine probably affected the metabolism of ATP to some extent. Furthermore, different bacteria possessed distinct SOD isoforms to cope with oxidative stress caused by nicotine. PMID:19294456

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Negative Regulation of Leptin-induced Reactive Oxygen Species (ROS) Formation by Cannabinoid CB1 Receptor Activation in Hypothalamic Neurons.

    Science.gov (United States)

    Palomba, Letizia; Silvestri, Cristoforo; Imperatore, Roberta; Morello, Giovanna; Piscitelli, Fabiana; Martella, Andrea; Cristino, Luigia; Di Marzo, Vincenzo

    2015-05-29

    The adipocyte-derived, anorectic hormone leptin was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of reactive oxygen species (ROS) levels in arcuate nucleus (ARC) neurons. Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity. Here we investigated the possibility of a negative regulation by CB1 receptors of leptin-mediated ROS formation in the ARC. Through pharmacological and molecular biology experiments we report data showing that leptin-induced ROS accumulation is 1) blunted by arachidonyl-2'-chloroethylamide (ACEA) in a CB1-dependent manner in both the mouse hypothalamic cell line mHypoE-N41 and ARC neuron primary cultures, 2) likewise blocked by a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, troglitazone, in a manner inhibited by T0070907, a PPAR-γ antagonist that also inhibited the ACEA effect on leptin, 3) blunted under conditions of increased endocannabinoid tone due to either pharmacological or genetic inhibition of endocannabinoid degradation in mHypoE-N41 and primary ARC neuronal cultures from MAGL(-/-) mice, respectively, and 4) associated with reduction of both PPAR-γ and catalase activity, which are reversed by both ACEA and troglitazone. We conclude that CB1 activation reverses leptin-induced ROS formation and hence possibly some of the ROS-mediated effects of the hormone by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity. This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

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    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.

  6. 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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    International Nuclear Information System (INIS)

    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

  10. Reactive oxygen species that activate c-Abl signaling trigger motoneuron death in non-cell-autonomous models of ALS

    Directory of Open Access Journals (Sweden)

    Fabiola eRojas

    2015-06-01

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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Rosacea, Reactive Oxygen Species, and Azelaic Acid

    OpenAIRE

    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...

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

    Science.gov (United States)

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

    2014-06-01

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

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  20. The effects of phorbol ester activation and reactive oxygen species scavengers on the macrophage-mediated foreign body reaction to polyurethanes.

    Science.gov (United States)

    McBane, Joanne E; Matheson, Loren A; Santerre, J Paul; Labow, Rosalind S

    2009-12-15

    Phorbol myristate acetate, a protein kinase C activator, inhibited monocyte-derived macrophage (MDM)-mediated degradation of aliphatic (HDI) polycarbonate-based polyurethanes but not degradation of the aromatic polycarbonate-based polyurethane (MDI). The objectives of this study were to determine if reactive oxygen species are involved in the phorbol myristate acetate effect on esterase activity and MDM-mediated polycarbonate-based polyurethane degradation and to find a good marker of material-initiated activation of MDM. The phorbol myristate acetate-dependent effects of the material chemistry on cell activation and degradation were evaluated by adding reactive oxygen species scavengers, catalase plus superoxide dismutase to MDM and assaying possible markers of MDM activation: esterase activity, acid phosphatase activity, and high molecular weight group box 1 protein (HMGB1). All treatments reduced the esterase activity in MDM on HDI but not in MDM on MDI. Acid phosphatase was inhibited in MDM to varying degrees on all surfaces by phorbol myristate acetate or catalase plus superoxide dismutase either alone or together. Secretion of HMGB1 from MDM on HDI431 was higher than MDI; however only secretion from MDM on HDI was inhibited by phorbol myristate acetate. In MDM on HDI, catalase plus superoxide dismutase reduced intracellular HMGB1 levels +/- phorbol myristate acetate; whereas, catalase, superoxide dismutase plus phorbol myristate acetate increased intracellular HMGB1 in MDM on MDI, suggesting that esterase and HMGB1 are more specific markers of activation than acid phosphatase. Manipulation of signaling pathways may provide insight surrounding the mechanism of activation for oxidative and/or hydrolytic degradative pathways in the MDM response to material surface chemistry.

  1. Synergistic effect of single-electron-trapped oxygen vacancies and carbon species on the visible light photocatalytic activity of carbon-modified TiO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaodong, E-mail: donguser@henu.edu.cn; Xue, Xiaoxiao; Liu, Xiaogang; Xing, Xing; Li, Qiuye; Yang, Jianjun

    2015-03-01

    Carbon-modified TiO{sub 2} (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), N{sub 2} 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 TiO{sub 2} 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 TiO{sub 2} 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.

  2. Physical exercise, reactive oxygen species and neuroprotection.

    Science.gov (United States)

    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

  3. Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation

    OpenAIRE

    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...

  4. Reactive oxygen species and redox compartmentalization

    OpenAIRE

    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...

  5. Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism

    NARCIS (Netherlands)

    Liemburg-Apers, D.C.; Willems, P.H.G.M.; Koopman, W.J.H.; Grefte, Sander

    2015-01-01

    Mitochondrial reactive oxygen species (ROS) production and detoxification are tightly balanced. Shifting this balance enables ROS to activate intracellular signaling and/or induce cellular damage and cell death. Increased mitochondrial ROS production is observed in a number of pathological condit

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

    Science.gov (United States)

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

    2004-05-15

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

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

    Science.gov (United States)

    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).

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  14. Antioxidant Activity/Capacity Measurement. 3. Reactive Oxygen and Nitrogen Species (ROS/RNS) Scavenging Assays, Oxidative Stress Biomarkers, and Chromatographic/Chemometric Assays.

    Science.gov (United States)

    Apak, Reşat; Özyürek, Mustafa; Güçlü, Kubilay; Çapanoğlu, Esra

    2016-02-10

    There are many studies in which the antioxidant potential of different foods have been analyzed. However, there are still conflicting results and lack of information as a result of unstandardized assay techniques and differences between the principles of the methods applied. The measurement of antioxidant activity, especially in the case of mixtures, multifunctional or complex multiphase systems, cannot be evaluated satisfactorily using a simple antioxidant test due to the many variables influencing the results. In the literature, there are many antioxidant assays that are used to measure the total antioxidant activity/capacity of food materials. In this review, reactive oxygen and nitrogen species (ROS/RNS) scavenging assays are evaluated with respect to their mechanism, advantages, disadvantages, and potential use in food systems. On the other hand, in vivo antioxidant activity (AOA) assays including oxidative stress biomarkers and cellular-based assays are covered within the scope of this review. Finally, chromatographic and chemometric assays are reviewed, focusing on their benefits especially with respect to their time saving, cost-effective, and sensitive nature.

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

    Science.gov (United States)

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

    2016-09-01

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

  16. Nicotine- and tar-free cigarette smoke induces cell damage through reactive oxygen species newly generated by PKC-dependent activation of NADPH oxidase.

    Science.gov (United States)

    Asano, Hiroshi; Horinouchi, Takahiro; Mai, Yosuke; Sawada, Osamu; Fujii, Shunsuke; Nishiya, Tadashi; Minami, Masabumi; Katayama, Takahiro; Iwanaga, Toshihiko; Terada, Koji; Miwa, Soichi

    2012-01-01

    We examined cytotoxic effects of nicotine/tar-free cigarette smoke extract (CSE) on C6 glioma cells. The CSE induced plasma membrane damage (determined by lactate dehydrogenase leakage and propidium iodide uptake) and cell apoptosis {determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] reduction activity and DNA fragmentation}. The cytotoxic activity decayed with a half-life of approximately 2 h at 37°C, and it was abolished by N-acetyl-L-cysteine and reduced glutathione. The membrane damage was prevented by catalase and edaravone (a scavenger of (•)OH) but not by superoxide dismutase, indicating involvement of (•)OH. In contrast, the CSE-induced cell apoptosis was resistant to edaravone and induced by authentic H(2)O(2) or O(2)(-) generated by the xanthine/xanthine oxidase system, indicating involvement of H(2)O(2) or O(2)(-) in cell apoptosis. Diphenyleneiodonium [NADPH oxidase (NOX) inhibitor] and bisindolylmaleimide I [BIS I, protein kinase C (PKC) inhibitor] abolished membrane damage, whereas they partially inhibited apoptosis. These results demonstrate that 1) a stable component(s) in the CSE activates PKC, which stimulates NOX to generate reactive oxygen species (ROS), causing membrane damage and apoptosis; 2) different ROS are responsible for membrane damage and apoptosis; and 3) part of the apoptosis is caused by oxidants independently of PKC and NOX. PMID:22302021

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

  19. Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation.

    Directory of Open Access Journals (Sweden)

    Naadiya Carrim

    Full Text Available We have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. In other cell systems, NOX-dependent ROS formation is facilitated by Pyk2, which along with its closely related homologue FAK are known to be activated and phosphorylated downstream of ligand binding to GPVI.To evaluate the relative roles of Pyk2 and FAK in GPVI-dependent ROS formation and to determine their location within the GPVI signaling pathway.Human and mouse washed platelets (from WT or Pyk2 KO mice were pre-treated with pharmacological inhibitors targeting FAK or Pyk2 (PF-228 and Tyrphostin A9, respectively and stimulated with the GPVI-specific agonist, CRP. FAK, but not Pyk2, was found to be essential for GPVI-dependent ROS production and aggregation. Subsequent human platelet studies with PF-228 confirmed FAK is essential for GPVI-mediated phosphatidylserine exposure, α-granule secretion (P-selectin (CD62P surface expression and integrin αIIbβ3 activation. To determine the precise location of FAK within the GPVI pathway, we analyzed the effect of PF-228 inhibition in CRP-stimulated platelets in conjunction with immunoprecipitation and pulldown analysis to show that FAK is downstream of Lyn, Spleen tyrosine kinase (Syk, PI3-K and Bruton's tyrosine kinase (Btk and upstream of Rac1, PLCγ2, Ca2+ release, PKC, Hic-5, NOX1 and αIIbβ3 activation.Overall, these data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway.

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

    Science.gov (United States)

    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

  1. Reactive oxygen species and mitogen-activated protein kinase induce apoptotic death of SH-SY5Y cells in response to fipronil.

    Science.gov (United States)

    Ki, Yeo-Woon; Lee, Jeong Eun; Park, Jae Hyeon; Shin, In Chul; Koh, Hyun Chul

    2012-05-20

    There are multiple lines of evidence showing that environmental toxicants including pesticides may contribute to neuronal cell death. Fipronil (FPN) is a phenylpyrazole insecticide that acts on insect GABA receptors. Although the action of FPN is restricted to insect neuronal or muscular transmitter systems, a few studies have assessed the effects of this neurotoxicant on neuronal cell death distinct from an insect. To determine the mechanisms underlying FPN-induced neuronal cell death, we evaluated the ability of this chemical to induce oxidative stress and studied the involvement of mitogen activated protein kinases (MAPKs) in FPN-induced apoptosis stress in human neuroblastoma SH-SY5Y (SH-SY5Y) cells. Exposure of SH-SY5Y cells to FPN led to the production of reactive oxygen species (ROS) and apoptotic cell death via activation of caspase-9 and caspase-3. Interestingly, the antioxidant, N-acetyl-cysteine (NAC) attenuated apoptotic cell death and ROS production induced by FPN. These results indicated that oxidative stress plays a central role in FPN-induced cytotoxicity. Mitochondrial complex I activity was also inhibited by FPN treatment. These finding indicate that FPN triggers intrinsic apoptosis via the mitochondrial signaling pathway that is initiated by the generation of ROS. Furthermore, FPN treatment induced phosphorylation of MAPK members. Activation of these protein kinases by FPN was involved in the onset of apoptosis as inhibitors specific to these kinases protect against FPN-induced cell death as well as ROS generation. Our data indicate that FPN-induced apoptosis is mediated primarily by the generation of ROS and activation of MAPK members followed by activation of the intrinsic apoptotic pathway.

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

    Science.gov (United States)

    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

  3. Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Long Shi

    Full Text Available Advanced Glycation End Products (AGEs has been implicated in the progression of diabetic keratopathy. However, details regarding their function are not well understood. In the present study, we investigated the effects of intracellular reactive oxygen species (ROS and JNK, p38 MAPK on AGE-modified bovine serum albumin (BSA induced Human telomerase-immortalized corneal epithelial cells (HUCLs apoptosis. We found that AGE-BSA induced HUCLs apoptosis and increased Bax protein expression, decreased Bcl-2 protein expression. AGE-BSA also induced the expression of receptor for advanced glycation end product (RAGE. AGE-BSA-RAGE interaction induced intracellular ROS generation through activated NADPH oxidase and increased the phosphorylation of p47phox. AGE-BSA induced HUCLs apoptosis was inhibited by pretreatment with NADPH oxidase inhibitors, ROS quencher N-acetylcysteine (NAC or neutralizing anti-RAGE antibodies. We also found that AGE-BSA induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked AGE-BSA-induced HUCLs apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by AGE-BSA. Our results indicate that AGE-BSA induced HUCLs apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.

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

    International Nuclear Information System (INIS)

    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

  5. Matrine induction of reactive oxygen species activates p38 leading to caspase-dependent cell apoptosis in non-small cell lung cancer cells.

    Science.gov (United States)

    Tan, Caihong; Qian, Xiaoqiang; Jia, Rongdi; Wu, Min; Liang, Zhongqin

    2013-11-01

    Non-small cell lung carcinoma (NSCLC) is one of the most refractory cancers in the clinic; it is insensitive to chemotherapy and is usually excised. However, screening natural compounds from herbs is also considered a possible method for its therapy. In the present study, we investigated whether matrine, a natural compound isolated from Sophora flavescens Ait. and exerting an inhibitory effect on lung cancer cells, also indicates inhibition on NSCLC cells and elucidated its molecular mechanism. Firstly, it is confirmed that matrine induces apoptosis of human NSCLC cells with anti-apoptotic factors inhibited and dependent on caspase activity. In addition, we found that matrine increases the phosphorylation of p38 but not its total protein, and inhibition of the p38 pathway with SB202190 partially prevents matrine-induced apoptosis. Furthermore, matrine generates reactive oxygen species (ROS) in a dose- and time-dependent manner, which is reversed by pretreatment with N-acetyl-L-cysteine (NAC). Additionally, inhibition of cell proliferation and increase of phosphorylation of p38 was also partially reversed by NAC. Collectively, matrine activates p38 pathway leading to a caspase-dependent apoptosis by inducing generation of ROS in NSCLC cells and may be a potential chemical for NSCLC.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Effects of exogenous nitric oxide on growth, active oxygen species metabolism, and photosynthetic characteristics in cucumber seedlings under NaCl stress

    Institute of Scientific and Technical Information of China (English)

    FAN Huaifu; GUO Shirong; JIAO Yansheng; ZHANG Runhua; LI Juan

    2007-01-01

    The study was conducted by means of nutrient solution culture to investigate the effects of exogenous nitric oxide (NO) on growth of cucumbe rseedlings,active oxygen species metabolism and photosynthetic characteristics in cucumber leaves under 50 mmol/L NaCl stress.The results showed that 10-400 μmol/L exogenous sodium nitroprusside (SNP),especially 100 μmol/L SNP,significantly alleviated the injury to seedlings and increased seedling growth.The activity of superoxide dismutase (SOD),peroxidase (POD),catalase (CAT),and ascorbate peroxidase (APX),and the contents of photosynthetic pigments and proline also increased under 50 mmol/L NaCI stress.Similarly,net photosynthetic rate (Pn),stomatal conductance (Gs),and transpiration rate (Tr) also increased significantly.However,exogenous nitric oxide application markedly decreased membrane permeahyde (MDA) and H2O2,and intercellular CO2 concentration (Ci) under 50 mmol/L NaCl stress.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

    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.

  10. Imaging reactive oxygen species in arthritis.

    Science.gov (United States)

    Chen, Wei-Tsung; Tung, Ching-Hsuan; Weissleder, Ralph

    2004-07-01

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

  11. Reactive oxygen species in redox cancer therapy.

    Science.gov (United States)

    Tong, Lingying; Chuang, Chia-Chen; Wu, Shiyong; Zuo, Li

    2015-10-10

    The role of reactive oxygen species (ROS) in cancer cells has been intensively studied for the past two decades. Cancer cells mostly have higher basal ROS levels than their normal counterparts. The induction of ROS has been shown to be associated with cancer development, metastasis, progression, and survival. Various therapeutic approaches targeting intracellular ROS levels have yielded mixed results. As widely accepted dietary supplements, antioxidants demonstrate both ROS scavenging ability and anti-cancer characteristics. However, antioxidants may not always be safe to use since excessive intake of antioxidants could lead to serious health concerns. In this review, we have evaluated the production and scavenging systems of ROS in cells, as well as the beneficial and harmful roles of ROS in cancer cells. We also examine the effect of antioxidants in cancer treatment, the effect of combined treatment of antioxidants with traditional cancer therapies, and the side effects of excessive antioxidant intake.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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...

  16. Production and Consumption of Reactive Oxygen Species by Fullerenes

    Science.gov (United States)

    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 ...

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

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    CERN Document Server

    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.

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

    Science.gov (United States)

    Hrycay, Eugene G; Bandiera, Stelvio M

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anantha eHarijith

    2014-09-01

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

  8. Mitochondrial-targeted fluorescent probes for reactive oxygen species

    OpenAIRE

    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...

  9. Balancing the generation and elimination of reactive oxygen species

    Science.gov (United States)

    Rodriguez, Rusty; Redman, Regina

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

  16. Active site densities, oxygen activation and adsorbed reactive oxygen in alcohol activation on npAu catalysts.

    Science.gov (United States)

    Wang, Lu-Cun; Friend, C M; Fushimi, Rebecca; Madix, Robert J

    2016-07-01

    The activation of molecular O2 as well as the reactivity of adsorbed oxygen species is of central importance in aerobic selective oxidation chemistry on Au-based catalysts. Herein, we address the issue of O2 activation on unsupported nanoporous gold (npAu) catalysts by applying a transient pressure technique, a temporal analysis of products (TAP) reactor, to measure the saturation coverage of atomic oxygen, its collisional dissociation probability, the activation barrier for O2 dissociation, and the facility with which adsorbed O species activate methanol, the initial step in the catalytic cycle of esterification. The results from these experiments indicate that molecular O2 dissociation is associated with surface silver, that the density of reactive sites is quite low, that adsorbed oxygen atoms do not spill over from the sites of activation onto the surrounding surface, and that methanol reacts quite facilely with the adsorbed oxygen atoms. In addition, the O species from O2 dissociation exhibits reactivity for the selective oxidation of methanol but not for CO. The TAP experiments also revealed that the surface of the npAu catalyst is saturated with adsorbed O under steady state reaction conditions, at least for the pulse reaction. PMID:27376884

  17. Mechanisms of nanotoxicity: Generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Peter P. Fu

    2014-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Luis Vitetta

    2015-09-01

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

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    The genome of the green sulfur bacterium Chlorobaculum (Cba.) tepidum, a strictly anaerobic photolithoautotroph, is predicted to encode more than ten genes whose products are potentially involved in protection from reactive oxygen species and an oxidative stress response. The encoded proteins...... insertionally inactivated. Wild-type Cba. tepidum cells were very sensitive to oxygen in the light but were remarkably resistant to oxygen in the dark. When wild-type and mutant cells were subjected to air for various times under dark or light condition, significant decreases in viability were detected in most...... defense against oxygen and reactive oxygen species. Reverse-transcriptase polymerase chain reaction studies showed that the genes with functions in oxidative stress protection were constitutively transcribed under anoxic growth conditions....

  2. Properties of Reactive Oxygen Species by Quantum Monte Carlo

    CERN Document Server

    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 ...

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

    Directory of Open Access Journals (Sweden)

    Kurt M. Sowers

    2010-01-01

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

  4. Decreased oxygen tension lowers reactive oxygen species and apoptosis and inhibits osteoblast matrix mineralization through changes in early osteoblast differentiation.

    Science.gov (United States)

    Nicolaije, Claudia; Koedam, Marijke; van Leeuwen, Johannes P T M

    2012-04-01

    Accumulating data show that oxygen tension can have an important effect on cell function and fate. We used the human pre-osteoblastic cell line SV-HFO, which forms a mineralizing extracellular matrix, to study the effect of low oxygen tension (2%) on osteoblast differentiation and mineralization. Mineralization was significantly reduced by 60-70% under 2% oxygen, which was paralleled by lower intracellular levels of reactive oxygen species (ROS) and apoptosis. Following this reduction in ROS the cells switched to a lower level of protection by down-regulating their antioxidant enzyme expression. The downside of this is that it left the cells more vulnerable to a subsequent oxidative challenge. Total collagen content was reduced in the 2% oxygen cultures and expression of matrix genes and matrix-metabolizing enzymes was significantly affected. Alkaline phosphatase activity and RNA expression as well as RUNX2 expression were significantly reduced under 2% oxygen. Time phase studies showed that high oxygen in the first phase of osteoblast differentiation and prior to mineralization is crucial for optimal differentiation and mineralization. Switching to 2% or 20% oxygen only during mineralization phase did not change the eventual level of mineralization. In conclusion, this study shows the significance of oxygen tension for proper osteoblast differentiation, extra cellular matrix (ECM) formation, and eventual mineralization. We demonstrated that the major impact of oxygen tension is in the early phase of osteoblast differentiation. Low oxygen in this phase leaves the cells in a premature differentiation state that cannot provide the correct signals for matrix maturation and mineralization.

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

    OpenAIRE

    Luis Vitetta; Samantha Coulson; Linnane, Anthony W.

    2015-01-01

    The production of intracellular reactive oxygen species and reactive nitrogen species has long been proposed as leading to the random deleterious modification of macromolecules (i.e., nucleic acids, proteins) with an associated progressive development of the age associated systemic diseases (e.g., diabetes, Parkinson’s disease) as well as contributing to the ageing process.   Superoxide anion (hydrogen peroxide) and nitric oxide (peroxynitrite) comprise regulated intracellular second messenge...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. Generator-specific targets of mitochondrial reactive oxygen species

    NARCIS (Netherlands)

    Bleier, L.; Wittig, I.; Heide, H.; Steger, M.; Brandt, U.; Drose, S.

    2015-01-01

    To understand the role of reactive oxygen species (ROS) in oxidative stress and redox signaling it is necessary to link their site of generation to the oxidative modification of specific targets. Here we have studied the selective modification of protein thiols by mitochondrial ROS that have been im

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-27

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

  10. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Chris M. Ireland

    2009-05-01

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

  12. 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.

    Science.gov (United States)

    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

  13. Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Maria Fátima Horta

    2012-01-01

    Full Text Available Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO, reactive oxygen species (ROS, and peroxynitrite (ONOO− in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response.

  14. Properties of reactive oxygen species by quantum Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 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.

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  18. Role of reactive oxygen species in the renal fibrosis

    Institute of Scientific and Technical Information of China (English)

    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.

  19. 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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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 ...

  3. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    OpenAIRE

    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...

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

    OpenAIRE

    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. ...

  5. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Subhashini Bolisetty

    2013-03-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. A novel herbal medicine, KIOM-C, induces autophagic and apoptotic cell death mediated by activation of JNK and reactive oxygen species in HT1080 human fibrosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Aeyung Kim

    Full Text Available KIOM-C was recently demonstrated to have anti-metastatic activity in highly malignant cancer cells via suppression of NF-κB-mediated MMP-9 activity. In addition, it was reported to be effective for clearance of the influenza virus by increasing production of anti-viral cytokines, such as TNF-α and IFN-γ, and efficacious in the treatment of pigs suffering from porcine circovirus-associated disease (PCVAD. In this study, we investigated whether KIOM-C induces cancer cell death and elucidated the underlying anti-cancer mechanisms. In addition, we examined whether KIOM-C oral administration suppresses in vivo tumor growth of HT1080 cells in athymic nude mice. We initially found that KIOM-C at concentrations of 500 and 1000 µg/ml caused dose- and time-dependent cell death in cancer cells, but not normal hepatocytes, to approximately 50% of control levels. At the early stage of KIOM-C treatment (12 h, cells were arrested in G1 phase, which was accompanied by up-regulation of p21 and p27, down-regulation of cyclin D1, and subsequent increases in apoptotic and autophagic cells. Following KIOM-C treatment, the extent of caspase-3 activation, PARP cleavage, Beclin-1 expression, and LC3-II conversion was remarkably up-regulated, but p62 expression was down-regulated. Phosphorylation of AMPK, ULK, JNK, c-jun, and p53 was increased significantly in response to KIOM-C treatment. The levels of intracellular ROS and CHOP expression were also increased. In particular, the JNK-specific inhibitor SP600125 blocked KIOM-C-induced ROS generation and CHOP expression almost completely, which consequently almost completely rescued cell death, indicating that JNK activation plays a critical role in KIOM-C-induced cell death. Furthermore, daily oral administration of 85 and 170 mg/kg KIOM-C efficiently suppressed the tumorigenic growth of HT1080 cells, without systemic toxicity. These results collectively suggest that KIOM-C efficiently induces cancer cell death by

  9. Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspases activation in human leukemia cells.

    Science.gov (United States)

    Cheng, An-Chin; Jian, Cheng-Bang; Huang, Yu-Ting; Lai, Ching-Shu; Hsu, Ping-Chi; Pan, Min-Hsiung

    2007-11-01

    Uncaria tomentosa (Wild.) DC., found in the Amazon rain forest in South-America and known commonly as cat's claw, has been used in traditional medicine to prevent and treat inflammation and cancer. Recently, it has been found to possess potent anti-inflammation activities. In this study, we extracted cat's claw using four different solvents of different polarities and compared their relative influence on proliferation in human premyelocytic leukemia HL-60 cell lines. Cat's claw n-hexane extracts (CC-H), ethyl acetate extracts (CC-EA) and n-butanol extracts (CC-B) had a greater anti-cancer effect on HL-60 cells than those extracted with methanol (CC-M). Furthermore, CC-EA induced DNA fragmentation in HL-60 cells in a clearly more a concentration- and time-dependent manner than the other extracts. CC-EA-induced cell death was characterized by cell body shrinkage and chromatin condensation. Further investigating the molecular mechanism behind CC-EA-induced apoptosis, sells treated with CC-EA underwent a rapid loss of mitochondrial transmembrane (DeltaPsi(m)) potential, stimulation of phosphatidylserine flip-flop, release of mitochondrial cytochrome c into cytosol, induction of caspase-3 activity in a time-dependent manner, and induced the cleavage of DNA fragmentation factor (DFF-45) and PARP poly-(ADP-ribose) polymerase (PARP). CC-EA promoted the up-regulation of Fas before the processing and activation of procaspase-8 and cleavage of Bid. In addition, the apoptosis induced by CC-EA was accompanied by up-regulation of Bax, down-regulation of Bcl-X(L) and cleavage of Mcl-1, suggesting that CC-EA may have some compounds that have anti-cancer activities and that further studies using cat's claw extracts need to be pursued. Taken together, the results of our studies show clearly that CC-EA's induction of apoptosis in HL-60 cells may make it very important in the development of medicine that can trigger chemopreventive actions in the body.

  10. 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.

    Science.gov (United States)

    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

  11. Antioxidant activity of Cat's whiskers flavonoid on some reactive oxygen and nitrogen species generating inflammatory cells is mediated by scavenging of free radicals

    Institute of Scientific and Technical Information of China (English)

    Asis Bala; Biswakanth Kar; Indrajit Karmakar; R.B.Suresh Kumar; Pallab Kanti Haldar

    2012-01-01

    AIM:To find out the effect of Cat's whiskers (Cleome gynandra L.,Capparidaceae) flavonoid (CWF) for the scavenging of free radicals in some inflammatory cells.METHODS:Mouse erythrocyte's hemoglobin,peritoneal macrophage,and peripheral blood lymphocytes were oxidized either by some of toxic chemicals (nitrite,carbon tetrachloride) or by enzymatic stimulation (glucoseoxidase) to produce oxidative damage to cells.The protective effect of the CWF was examined,and the biochemical mechanism of action was also investigated in terms of the scavenging of free radicals.RESULTS:CWF (1-20 μg·mL-1) decreased glucoseoxidase and nitrite induce oxidative damage in a concentration dependent manner in an in vitro model and inhibited the lysis of RBC [(28.64 ±13.03)% and (70.31 ± 1.80)%] when mice were treated with CWF (25 and 50 mg·kg-1).To assess the antioxidant potential of CWF in the lymphocytes and macrophages in living animals,the effect of CWF was measured on the elevated level of superoxide anions production in the cells.CWF scavenged the superoxide anion (O2-) production and inhibited the O2-induced destruction of protein and lipid biomolecules.CONCLUSION:The study has established that the CWF mediates its antioxidant activity in some chronic inflammatory cells via its free radical scavenging activity.

  12. Reactive Oxygen Species in Vascular Formation and Development

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    Yijiang Zhou

    2013-01-01

    Full Text Available Reactive oxygen species (ROS are derived from the metabolism of oxygen and are traditionally viewed as toxic byproducts that cause damage to biomolecules. It is now becoming widely acknowledged that ROS are key modulators in a variety of biological processes and pathological states. ROS mediate key signaling transduction pathways by reversible oxidation of certain signaling components and are involved in the signaling of growth factors, G-protein-coupled receptors, Notch, and Wnt and its downstream cascades including MAPK, JAK-STAT, NF-κB, and PI3K/AKT. Vascular formation and development is one of the most important events during embryogenesis and is vital for postnasal tissue repair. In this paper, we will discuss how ROS regulate different steps in vascular development, including smooth muscle cell differentiation, angiogenesis, endothelial progenitor cells recruitment, and vascular cell migration.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Implications for reactive oxygen species in schizophrenia pathogenesis.

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-05-01

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

  16. Myoglobin oxygenation and autoxidation in three reptilian species.

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Robin Julie Schneider

    2016-03-01

    Full Text Available 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

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

    Science.gov (United States)

    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[Formula: see text]) 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[Formula: see text] 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 O[Formula: see text] and H2O2 was examined by measuring recovery of O[Formula: see text] and H2O2 added to the influent medium. O[Formula: see text] production rates ranged from undetectable to 7.3 × 10(-16) mol cell(-1) h(-1), while H2O2 production rates ranged from undetectable to 3.4 × 10(-16) mol cell(-1) h(-1). Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O[Formula: see text] in light than dark, even when the organisms were killed, indicating that O[Formula: see text] is produced via a passive photochemical process on the cell surface. The ratio of H2O2 to O[Formula: see text] production rates was consistent with production of H2O2 solely through dismutation of O[Formula: see text] for T. oceanica, while T. pseudonana made much more H2O2 than O[Formula: see text]. 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% O[Formula: see text]) were consistently higher than those for live cultures (65-95% H2O2; 10-50% O[Formula: see text]). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  5. Reactive oxygen species in organ-specific autoimmunity.

    Science.gov (United States)

    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

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

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    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.

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

    Science.gov (United States)

    Mohsenzadegan, Monireh; Mirshafiey, Abbas

    2012-09-01

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

  8. FREE RADICALS, REACTIVE OXYGEN SPECIES, OXIDATIVE STRESSES AND THEIR CLASSIFICATIONS.

    Science.gov (United States)

    Lushchak, V I

    2015-01-01

    The phrases "free radicals" and "reactive oxygen species" (ROS) are frequently used interchangeably although this is not always correct. This article gives a brief description of two mentioned oxygen forms. During the first two-three decades after ROS discovery in biological systems (1950-1970 years) they were considered only as damaging agents, but later their involvement in organism protection and regulation of the expression of certain genes was found. The physiological state of increased steady-state ROS level along with certain physiological effects has been called oxidative stress. This paper describes ROS homeostasis and provides several classifications of oxidative stresses. The latter are based on time-course and intensity principles. Therefore distinguishing between acute and chronic stresses on the basis of the dynamics, and the basal oxidative stress, low intensity oxidative stress, strong oxidative stress, and finally a very strong oxidative stress based on the intensity of the action of the inductor of the stress are described. Potential areas of research include the development of this field with complex classification of oxidative stresses, an accurate identification of cellular targets of ROS action, determination of intracellular spatial and temporal distribution of ROS and their effects, deciphering the molecular mechanisms responsible for cell response to ROS attacks, and their participation in the normal cellular functions, i.e. cellular homeostasis and its regulation.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    van der Wijst, Monique

    2016-01-01

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

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. 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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

    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

  18. Genetically encoded reactive oxygen species (ROS) and redox indicators.

    Science.gov (United States)

    Pouvreau, Sandrine

    2014-02-01

    Redox processes are increasingly being recognized as key elements in the regulation of cellular signaling cascades. They are frequently encountered at the frontier between physiological functions and pathological events. The biological relevance of intracellular redox changes depends on the subcellular origin, the spatio-temporal distribution and the redox couple involved. Thus, a key task in the elucidation of the role of redox reactions is the specific and quantitative measurement of redox conditions with high spatio-temporal resolution. Unfortunately, until recently, our ability to perform such measurements was limited by the lack of adequate technology. Over the last 10 years, promising imaging tools have been developed from fluorescent proteins. Genetically encoded reactive oxygen species (ROS) and redox indicators (GERRIs) have the potential to allow real-time and pseudo-quantitative monitoring of specific ROS and thiol redox state in subcellular compartments or live organisms. Redox-sensitive yellow fluorescent proteins (rxYFP family), redox-sensitive green fluorescent proteins (roGFP family), HyPer (a probe designed to measure H2 O2 ), circularly permuted YFP and others have been used in several models and sufficient information has been collected to highlight their main characteristics. This review is intended to be a tour guide of the main types of GERRIs, their origins, properties, advantages and pitfalls.

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

    Directory of Open Access Journals (Sweden)

    Noah C. Jenkins

    2013-01-01

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

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

    Science.gov (United States)

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

    2011-10-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Reactive oxygen species induced structural alterations of substance P

    Directory of Open Access Journals (Sweden)

    Y. T. Konttinen

    1992-01-01

    Full Text Available Substance P (SP1-11 was exposed to a continuous flux of superoxide (O2- or hydroxyl radicals (.OH in a hypoxanthine (HX/xanthine oxidase (86 mU system in the presence of 1 mM deferoxamine and 40 mM D-mannitol or 50 μM FeCI3. 6H2O and 50 μM EDTA, respectively. O2- caused fragmentation between the Phe7 and Phe8, whereas .OH induced cleavage also between the Phe8 and Gly9. Reactive oxygen species H2O2 and HCIO did not cause fragmentation, but modification of the amino acid side chains and/or aggregation with altered hydrophobicity in reverse phase high performance liquid chromatography compared to native SP1-11. Furthermore, exposure of SP1-11 to phorbol myristate acetate preactivated neutrophils resuited in products similar to those observed upon exposure to superoxide or hydroxyl radicals in a cell-free HX/xanthine oxidase system. This study suggests that, in contrast to rigid proteins, fragmentation is relatively easily induced in a small peptide like SP1-11, perhaps due to strain on the peptide and t-carbon bonds caused by the movable, random coil configuration acquired by SP1-11 in an aqueous solution. Oxidative modification might modulate paracrine actions of SP1-11 at site of inflammation.

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

    Science.gov (United States)

    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

  4. Reactive Oxygen Species Tune Root Tropic Responses1[OPEN

    Science.gov (United States)

    Krieger, Gat

    2016-01-01

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

  5. Are mitochondrial reactive oxygen species required for autophagy?

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-19

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Rachel McCormick

    2016-08-01

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

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

    Science.gov (United States)

    Chisté, Renan Campos; Mercadante, Adriana Zerlotti; Gomes, Ana; Fernandes, Eduarda; Lima, José Luís Fontes da Costa; Bragagnolo, Neura

    2011-07-15

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

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

    Science.gov (United States)

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

    OpenAIRE

    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,...

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

  15. Radiation induces aerobic glycolysis through reactive oxygen species

    International Nuclear Information System (INIS)

    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

  16. Action of reactive oxygen species in the antifungal mechanism of gemini-pyridinium salts against yeast.

    Science.gov (United States)

    Shirai, Akihiro; Ueta, Shouko; Maseda, Hideaki; Kourai, Hiroki; Omasa, Takeshi

    2012-06-01

    We previously found that the gemini quaternary salt (gemini-QUAT) containing two pyridinium residues per molecule, 3,3'- (2,7-dioxaoctane) bis (1-decylpyridinium bromide) (3DOBP-4,10) , exerted fungicidal activity against Saccharomyces cerevisiae and caused respiration inhibition and the cytoplasmic leakage of ATP, magnesium, and potassium ions. Here, we investigated how the gemini-QUAT, 3DOBP-4,10, exerts more powerful antimicrobial activity than the mono-QUAT N-cetylpyridinium chloride (CPC) and examined the association between reactive oxygen species (ROS) and the antimicrobial mechanism. Antifungal assays showed that the activity of 3DOBP-4,10 against two yeasts, S. cerevisiae and Candida albicans, was significantly elevated under aerobic conditions, and largely reduced under anaerobic conditions (nitrogen atmosphere) . Adding radical scavengers such as superoxide dismutase, catalase and potassium iodide (KI) also decreased the fungicidal activity of 3DOBP-4,10 but negligibly affected that of CPC. We measured survival under static conditions and found that the rapid fungicidal profile of 3DOBP-4,10 was lost, whereas that of CPC was slightly affected in the presence of KI. Our results suggest that 3DOBP-4,10 exerts powerful antimicrobial activity by penetrating the cell wall and membrane, which then allows oxygen to enter the cells, where it participates in the generation of intracellular ROS. The activity could thus be attributable to a synergic antimicrobial combination of the disruption of organelle membranes by the QUAT and oxidative stress imposed by ROS. PMID:22790843

  17. DNA Evidence Uncompromised by Active Oxygen

    Directory of Open Access Journals (Sweden)

    Ana Castelló

    2010-01-01

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

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

    OpenAIRE

    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...

  19. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

  4. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    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)

  6. Roles of Reactive Oxygen and Nitrogen Species in Pain

    OpenAIRE

    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...

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

    Science.gov (United States)

    Blackstone, N W

    2001-06-01

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

  8. Comparisons of early transcriptome responses to low-oxygen environments in three dicotyledonous plant species

    Science.gov (United States)

    Christianson, Jed A; Llewellyn, Danny J; Dennis, Elizabeth S

    2010-01-01

    Waterlogging is a serious impediment to crop productivity worldwide which acts to reduce oxygen levels in the rhizosphere due to the low diffusion rate of molecular oxygen in water. Plants respond to low oxygen through rapid and specific changes at both the transcriptional and translational levels. Transcriptional changes to low-oxygen (hypoxia) stress have been studied in a number of plant species using whole genome microarrays. Using transcriptome data from root tissue from early time points (4–5 h) from cotton (Gossypium hirsutum), Arabidopsis and gray poplar (Populus x canescens), we have identified a core set of orthologous genes that responded to hypoxia in similar ways between species, and others that showed species specific responses. Responses to hypoxia were most similar between Arabidopsis and cotton, while the waterlogging tolerant poplar species exhibited some significant differences. PMID:20724824

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

    Science.gov (United States)

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

  10. Binding of Reactive Oxygen Species at Fe-S Cubane Clusters.

    Science.gov (United States)

    Bruska, Marta K; Stiebritz, Martin T; Reiher, Markus

    2015-12-21

    Reactive oxygen species (ROS) play an important role in the biochemistry of the cell and occur in degenerative processes as well as in signal transduction. Iron-sulfur proteins are particularly oxygen-sensitive and their inorganic cofactors frequently undergo ROS-induced decomposition reactions. As experimental knowledge about these processes is still incomplete we present here a quantum chemical study of the relative energetics for the binding of the most relevant ROS to [Fe4S4] clusters. We find that cubane clusters with one uncoordinated Fe atom (as found, for instance, in aconitase) bind all oxygen derivatives considered, whereas activation of triplet O2 to singlet O2 is required for binding to valence-saturated iron centers in these clusters. The radicals NO and OH feature the most exothermic binding energies to Fe atoms. Direct sulfoxidation of coordinating cysteine residues is only possible by OH or H2O2 as attacking agents. The thermodynamic picture of ROS binding to iron-sulfur clusters established here can serve as a starting point for studying reactivity-modulating effects of the cluster-embedding protein environment on ROS-induced decomposition of iron-sulfur proteins. PMID:26585994

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

    Science.gov (United States)

    Allertz, Carl; Selleby, Malin; Sichen, Du

    2016-10-01

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

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

    Science.gov (United States)

    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.

  13. Regulatory volume decrease in cardiomyocytes is modulated by calcium influx and reactive oxygen species.

    Science.gov (United States)

    Rojas-Rivera, Diego; Díaz-Elizondo, Jessica; Parra, Valentina; Salas, Daniela; Contreras, Ariel; Toro, Barbra; Chiong, Mario; Olea-Azar, Claudio; Lavandero, Sergio

    2009-11-01

    We investigated the role of Ca(2+) in generating reactive oxygen species (ROS) induced by hyposmotic stress (Hypo) and its relationship to regulatory volume decrease (RVD) in cardiomyocytes. Hypo-induced increases in cytoplasmic and mitochondrial Ca(2+). Nifedipine (Nife) inhibited both Hypo-induced Ca(2+) and ROS increases. Overexpression of catalase (CAT) induced RVD and a decrease in Hypo-induced blebs. Nife prevented CAT-dependent RVD activation. These results show a dual role of Hypo-induced Ca(2+) influx in the control of cardiomyocyte viability. Hypo-induced an intracellular Ca(2+) increase which activated RVD and inhibited necrotic blebbing thus favoring cell survival, while simultaneously increasing ROS generation, which in turn inhibited RVD and induced necrosis.

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

    Science.gov (United States)

    Kuchitsu, Kazuyuki

    2013-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2009-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-01

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

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

    DEFF Research Database (Denmark)

    Hebelstrup, Kim; Møller, Ian Max

    2015-01-01

    Hypoxia commonly occurs in roots in water-saturated soil and in maturing and germinating seeds. We here review the role of the mitochondria in the cellular response to hypoxia with an emphasis on the turnover of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and their potential...... signaling function. Under hypoxia, aerobic respiration in the mitochondria can be limited by the oxygen supply, the electron transport component are more reduced and superoxide and NO are produced in increasing amounts at Complexes III and IV initiating the formation of a range of other ROS and RNS. Unless...

  19. Reactive species formed on proteins exposed to singlet oxygen

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan

    2004-01-01

    for (1)O(2), with damage occurring preferentially at Trp, His, Tyr, Met, and Cys side-chains. Reaction with each of these residues gives rise to further reactive species. In the case of Trp and Tyr, initial poorly characterised endoperoxides are believed to undergo ring-opening reactions to give...... 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...... 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 species...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  2. 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.

    Science.gov (United States)

    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

  3. Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.

    Directory of Open Access Journals (Sweden)

    Zhen Li

    Full Text Available OBJECTIVE: Mitochondrial oxidative stress is the basis for pancreatic β-cell apoptosis and a common pathway for numerous types of damage, including glucotoxicity and lipotoxicity. We cultivated mice pancreatic β-cell tumor Min6 cell lines in vitro and observed pancreatic β-cell apoptosis and changes in mitochondrial function before and after the addition of Exendin-4. Based on these observations, we discuss the protective role of Exendin-4 against mitochondrial oxidative damage and its relationship with Ca(2+-independent phospholipase A2. METHODS: We established a pancreatic β-cell oxidative stress damage model using Min6 cell lines cultured in vitro with tert-buty1 hydroperoxide and hydrogen peroxide. We then added Exendin-4 to observe changes in the rate of cell apoptosis (Annexin-V-FITC-PI staining flow cytometry and DNA ladder. We detected the activity of the caspase 3 and 8 apoptotic factors, measured the mitochondrial membrane potential losses and reactive oxygen species production levels, and detected the expression of cytochrome c and Smac/DLAMO in the cytosol and mitochondria, mitochondrial Ca2-independent phospholipase A2 and Ca(2+-independent phospholipase A2 mRNA. RESULTS: The time-concentration curve showed that different percentages of apoptosis occurred at different time-concentrations in tert-buty1 hydroperoxide- and hydrogen peroxide-induced Min6 cells. Incubation with 100 µmol/l of Exendin-4 for 48 hours reduced the Min6 cell apoptosis rate (p<0.05. The mitochondrial membrane potential loss and total reactive oxygen species levels decreased (p<0.05, and the release of cytochrome c and Smac/DLAMO from the mitochondria was reduced. The study also showed that Ca(2+-independent phospholipase A2 activity was positively related to Exendin-4 activity. CONCLUSION: Exendin-4 reduces Min6 cell oxidative damage and the cell apoptosis rate, which may be related to Ca(2-independent phospholipase A2.

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

    Science.gov (United States)

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

    2015-12-01

    Exposure of phytoplankton to the water-accommodated fraction of crude oil can elicit a number of stress responses, but the mechanisms that drive these responses are unclear. South Louisiana crude oil was selected to investigate its effects on population growth, chlorophyll a (Chl a) content, antioxidative defense, and lipid peroxidation, for the marine diatom, Ditylum brightwellii, and the dinoflagellate, Heterocapsa triquetra, in laboratory-based microcosm experiments. The transcript levels of several possible stress-responsive genes in D. brightwellii were also measured. The microalgae were exposed to crude oil for up to 96 h, and Chl a content, superoxide dismutase (SOD), the glutathione pool (GSH and GSSG), and lipid peroxidation content were analyzed. The cell growth of both phytoplankton species was inhibited with increasing crude oil concentrations. Crude oil exposure did not affect Chl a content significantly in cells. SOD activities showed similar responses in both species, being enhanced at 4- and 8-mg/L crude oil exposure. Only H. triquetra demonstrated enhanced activity in GSSG pool and lipid peroxidation at 8-mg/L crude oil exposure, suggesting that phytoplankton species have distinct physiological responses and tolerance levels to crude oil exposure. This study indicated the activation of reactive oxygen species (ROS) in phytoplankton under crude oil exposure; however, the progressive damage in cells is still unknown. Thus, ROS-related damage in nucleic acid, lipids, proteins, and DNA, due to crude oil exposure could be a worthwhile subject of study to better understand crude oil toxicity at the base of the food web. PMID:26206126

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

    Science.gov (United States)

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

    2006-09-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Reactive oxygen species-responsive protein modification and its intracellular delivery for targeted cancer therapy.

    Science.gov (United States)

    Wang, Ming; Sun, Shuo; Neufeld, Caleb I; Perez-Ramirez, Bernardo; Xu, Qiaobing

    2014-12-01

    Herein we report a convenient chemical approach to reversibly modulate protein (RNase A) function and develop a protein that is responsive to reactive oxygen species (ROS) for targeted cancer therapy. The conjugation of RNase A with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl carbonate (NBC) blocks protein lysine and temporarily deactivates the protein. However, the treatment of RNase A-NBC with hydrogen peroxide (one major intracellular ROS) efficiently cleaves the NBC conjugation and restores the RNase A activity. Thus, RNase A-NBC can be reactivated inside tumor cells by high levels of intracellular ROS, thereby restoring the cytotoxicity of RNase A for cancer therapy. Due to higher ROS levels inside tumor cells compared to healthy cells, and the resulting different levels of RNase A-NBC reactivation, RNase A-NBC shows a significant specific cytotoxicity against tumor cells.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2011-01-01

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

  11. The role of beaded activated carbon's surface oxygen groups on irreversible adsorption of organic vapors.

    Science.gov (United States)

    Jahandar Lashaki, Masoud; Atkinson, John D; Hashisho, Zaher; Phillips, John H; Anderson, James E; Nichols, Mark

    2016-11-01

    The objective of this study is to determine the contribution of surface oxygen groups to irreversible adsorption (aka heel formation) during cyclic adsorption/regeneration of organic vapors commonly found in industrial systems, including vehicle-painting operations. For this purpose, three chemically modified activated carbon samples, including two oxygen-deficient (hydrogen-treated and heat-treated) and one oxygen-rich sample (nitric acid-treated) were prepared. The samples were tested for 5 adsorption/regeneration cycles using a mixture of nine organic compounds. For the different samples, mass balance cumulative heel was 14 and 20% higher for oxygen functionalized and hydrogen-treated samples, respectively, relative to heat-treated sample. Thermal analysis results showed heel formation due to physisorption for the oxygen-deficient samples, and weakened physisorption combined with chemisorption for the oxygen-rich sample. Chemisorption was attributed to consumption of surface oxygen groups by adsorbed species, resulting in formation of high boiling point oxidation byproducts or bonding between the adsorbates and the surface groups. Pore size distributions indicated that different pore sizes contributed to heel formation - narrow micropores (<7Å) in the oxygen-deficient samples and midsize micropores (7-12Å) in the oxygen-rich sample. The results from this study help explain the heel formation mechanism and how it relates to chemically tailored adsorbent materials. PMID:27295065

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Efficient oxygen electrocatalysis on special active sites

    DEFF Research Database (Denmark)

    Halck, Niels Bendtsen

    is used to explain the increase in activity observed for the OER catalyst ruthenium dioxide when it is mixed with nickel or cobalt. Manganese and cobalt oxides when in the vicinity of gold also display an increase in OER activity which can be explained by locally created special active sites. Density...

  14. Enhancing Activity for the Oxygen Evolution Reaction

    DEFF Research Database (Denmark)

    Frydendal, Rasmus; Busch, Michael; Halck, Niels Bendtsen;

    2014-01-01

    of all reaction intermediates cannot be optimized individually. However, experimental investigations have shown that drastic improvements can be realized for manganese and cobalt-based oxides if gold is added to the surface or used as substrate. We propose an explanation for these enhancements based...... that the oxygen evolution reaction overpotential decreases by 100–300 mV for manganese oxides and 100 mV for cobalt oxides....... on a hydrogen acceptor concept. This concept comprises a stabilization of an *-OOH intermediate, which effectively lowers the potential needed for breaking bonds to the surface. On this basis, we investigate the interactions between the oxides and gold by using DFT calculations. The results suggest...

  15. Texas Endangered Species Activity Book.

    Science.gov (United States)

    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.…

  16. Green Oxygenation Degradation of Rhodamine B by Using Activated Molecule Oxygen

    Institute of Scientific and Technical Information of China (English)

    Ke Jian DENG; Fei HUANG; Duo Yuan WANG; Zheng He PENG; Yun Hong ZHOU

    2004-01-01

    Iron(Ⅱ) tetra-(1,4-dithin)-porphyrazine, (FePz(dtn)4) is able to activate molecule oxygen for oxygenation degradation of rhodamine B (RhB) in an extensive pH region without light excitation. Experiments indicate that the RhB can be degraded nearly 52% in alkaline aqueous solution, bubbling with dioxygen for seven hours in the presence of FePz(dtn)4 and the hydrogen peroxides as an actve intermediate were determined by DPD method. The catalyst is recyclable and the catalyst activity was maintained after l0 recycles.

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

    Directory of Open Access Journals (Sweden)

    Berlinda Verdoodt

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

  18. Ligation of Glycophorin A Generates Reactive Oxygen Species Leading to Decreased Red Blood Cell Function

    Science.gov (United States)

    Khoory, Joseph; Estanislau, Jessica; Elkhal, Abdallah; Lazaar, Asmae; Melhorn, Mark I.; Brodsky, Abigail; Illigens, Ben; Hamachi, Itaru; Kurishita, Yasutaka; Ivanov, Alexander R.; Shevkoplyas, Sergey; Shapiro, Nathan I.; Ghiran, Ionita C.

    2016-01-01

    Acute, inflammatory conditions associated with dysregulated complement activation are characterized by significant increases in blood concentration of reactive oxygen species (ROS) and ATP. The mechanisms by which these molecules arise are not fully understood. In this study, using luminometric- and fluorescence-based methods, we show that ligation of glycophorin A (GPA) on human red blood cells (RBCs) results in a 2.1-fold, NADPH-oxidase-dependent increase in intracellular ROS that, in turn, trigger multiple downstream cascades leading to caspase-3 activation, ATP release, and increased band 3 phosphorylation. Functionally, using 2D microchannels to assess membrane deformability, GPS-ligated RBCs travel 33% slower than control RBCs, and lipid mobility was hindered by 10% using fluorescence recovery after photobleaching (FRAP). These outcomes were preventable by pretreating RBCs with cell-permeable ROS scavenger glutathione monoethyl ester (GSH-ME). Our results obtained in vitro using anti-GPA antibodies were validated using complement-altered RBCs isolated from control and septic patients. Our results suggest that during inflammatory conditions, circulating RBCs significantly contribute to capillary flow dysfunctions, and constitute an important but overlooked source of intravascular ROS and ATP, both critical mediators responsible for endothelial cell activation, microcirculation impairment, platelet activation, as well as long-term dysregulated adaptive and innate immune responses. PMID:26784696

  19. Preliminary study on overproduction of reactive oxygen species by neutrophils in diabetes mellitus

    Science.gov (United States)

    Ridzuan, Noridzzaida; John, Cini Mathew; Sandrasaigaran, Pratheep; Maqbool, Maryam; Liew, Lee Chuen; Lim, Jonathan; Ramasamy, Rajesh

    2016-01-01

    AIM: To assess the amount and pattern of reactive oxygen species (ROS) production in diabetic patient-derived neutrophils. METHODS: Blood samples from type 2 diabetes mellitus (DM) patients and volunteers (controls) were subjected to neutrophil isolation and the assessment of neutrophil oxidative burst using chemiluminescence assay. Neutrophils were activated by using phorbol myristate acetate (PMA) and neutrophils without activation were kept as a negative control. The chemiluminescence readings were obtained by transferring cell suspension into a 1.5 mL Eppendorf tube, with PMA and luminol. Reaction mixtures were gently vortexed and placed inside luminometer for a duration of 5 min. RESULTS: Our results showed that in the resting condition, the secretion of ROS in normal non-diabetic individuals was relatively low compared to diabetic patients. However, the time scale observation revealed that the secreted ROS declined accordingly with time in non-diabetic individuals, yet such a reduction was not detected in diabetic patients where at all the time points, the secretion of ROS was maintained at similar magnitudes. This preliminary study demonstrated that ROS production was significantly higher in patients with DM compared to non-diabetic subjects in both resting and activated conditions. CONCLUSION: The respiratory burst activity of neutrophils could be affected by DM and the elevation of ROS production might be an aggravating factor in diabetic-related complications. PMID:27433296

  20. Reactive oxygen species metabolism during the cadmium hyperaccumulation of a new hyperaccumulator Sedum alfredii (Crassulaceae).

    Science.gov (United States)

    Zhang, Zhong-chun; Qiu, Bao-Sheng

    2007-01-01

    Sedum alfredii Hance, a newly discovered hyperaccumulator, could serve as a good material for phytoremediation of Cd polluted sites. Malondialdehyde (MDA), reactive oxygen species (ROS) and antioxidases (catalase (CAT); superoxide dismutase (SOD); peroxidase (POD)) in the leaf were determined when S. alfredii was treated for 15 d with various CdCl2 concentrations ranging from 0 to 800 micromol/L. The results showed that the production rate of 2',7'-dichlorofluorescein (DCF), which is an indicator of ROS level, reached up to the maximum at 400 micromol/L CdCl2 and then declined with the increase of CdCl2 concentration, while MDA accumulation tended to increase. CAT activity was significantly inhibited at all tested CdCl2 concentrations and SOD activity was sharply suppressed at 800 micromol/L CdCl2. However, the enhancement of POD activity was observed when CdCl2 concentration was higher than 400 micromol/L. In addition, its activity increased when treated with 600 micromol/L CdCl2 for more than 5 d. When sodium benzoate, a free radical scavenger, was added, S. alfredii was a little more sensitive to Cd toxicity than that exposed to Cd alone, and the Cd accumulation tended to decline with the increase of sodium benzoate concentration. It came to the conclusions that POD played an important role during Cd hyperaccumulation, and the accumulation of ROS induced by Cd treatment might be involved in Cd hyperaccumulation. PMID:18232224

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

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Stefanie; Sommer, Anja [Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen (Germany); Distel, Luitpold V.R. [Department of Radiation Oncology, Friedrich Alexander University Erlangen-Nuremberg, Universitaetsstrasse 27, D-91054 Erlangen (Germany); Neuhuber, Winfried [Department of Anatomy, Chair of Anatomy I, Friedrich Alexander University Erlangen-Nuremberg, Krankenhausstr. 9, D-91054 Erlangen (Germany); Kryschi, Carola, E-mail: kryschi@chemie.uni-erlangen.de [Department of Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, D-91058 Erlangen (Germany)

    2012-08-24

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

  2. Transcription factors that defend bacteria against reactive oxygen species

    OpenAIRE

    Imlay, James A.

    2015-01-01

    Bacteria live in a toxic world in which their competitors excrete hydrogen peroxide or superoxide-generating redox-cycling compounds. They protect themselves by activating regulons controlled by the OxyR, PerR, and SoxR transcription factors. OxyR and PerR sense peroxide when it oxidizes key thiolate or iron moieties, respectively; they then induce overlapping sets of proteins that defend their vulnerable metalloenzymes. An additional role for OxyR in detecting electrophilic compounds is poss...

  3. AMPK signaling in skeletal muscle during exercise: Role of reactive oxygen and nitrogen species.

    Science.gov (United States)

    Morales-Alamo, David; Calbet, Jose A L

    2016-09-01

    Reactive oxygen and nitrogen species (RONS) are generated during exercise depending on intensity, duration and training status. A greater amount of RONS is released during repeated high-intensity sprint exercise and when the exercise is performed in hypoxia. By activating adenosine monophosphate-activated kinase (AMPK), RONS play a critical role in the regulation of muscle metabolism but also in the adaptive responses to exercise training. RONS may activate AMPK by direct an indirect mechanisms. Directly, RONS may activate or deactivate AMPK by modifying RONS-sensitive residues of the AMPK-α subunit. Indirectly, RONS may activate AMPK by reducing mitochondrial ATP synthesis, leading to an increased AMP:ATP ratio and subsequent Thr(172)-AMPK phosphorylation by the two main AMPK kinases: LKB1 and CaMKKβ. In presence of RONS the rate of Thr(172)-AMPK dephosphorylation is reduced. RONS may activate LKB1 through Sestrin2 and SIRT1 (NAD(+)/NADH.H(+)-dependent deacetylase). RONS may also activate CaMKKβ by direct modification of RONS sensitive motifs and, indirectly, by activating the ryanodine receptor (Ryr) to release Ca(2+). Both too high (hypoxia) and too low (ingestion of antioxidants) RONS levels may lead to Ser(485)-AMPKα1/Ser(491)-AMPKα2 phosphorylation causing inhibition of Thr(172)-AMPKα phosphorylation. Exercise training increases muscle antioxidant capacity. When the same high-intensity training is applied to arm and leg muscles, arm muscles show signs of increased oxidative stress and reduced mitochondrial biogenesis, which may be explained by differences in RONS-sensing mechanisms and basal antioxidant capacities between arm and leg muscles. Efficient adaptation to exercise training requires optimal exposure to pulses of RONS. Inappropriate training stimulus may lead to excessive RONS formation, oxidative inactivation of AMPK and reduced adaptation or even maladaptation. Theoretically, exercise programs should be designed taking into account the

  4. Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

    Directory of Open Access Journals (Sweden)

    Marianna Guida

    2014-01-01

    Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-03-17

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

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

    Science.gov (United States)

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

    2015-03-17

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-04-01

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

  9. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis

    Science.gov (United States)

    Tse, Gary; Yan, Bryan P.; Chan, Yin W. F.; Tian, Xiao Yu; Huang, Yu

    2016-01-01

    Background: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS), which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis. Method: A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function, remodeling and arrhythmogenesis. Results: Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS, which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation of mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signaling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP). Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signaling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry. Conclusion: ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension, and heart failure. PMID:27536244

  10. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge

    Directory of Open Access Journals (Sweden)

    Yu-Chiang Hung

    2016-01-01

    Full Text Available Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen. Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

  11. Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction.

    Science.gov (United States)

    Usatyuk, Peter V; Kotha, Sainath R; Parinandi, Narasimham L; Natarajan, Viswanathan

    2013-01-01

    Reactive oxygen species (ROS) have emerged as critical players in the pathophysiology of pulmonary disorders and diseases. Earlier, we have demonstrated that ROS stimulate lung endothelial cell (EC) phospholipase D (PLD) that generates phosphatidic acid (PA), a second messenger involved in signal transduction. In the current study, we investigated the role of PLD signaling in the ROS-induced lung vascular EC barrier dysfunction. Our results demonstrated that hydrogen peroxide (H2O2), a typical physiological ROS, induced PLD activation and altered the barrier function in bovine pulmonary artery ECs (BPAECs). 1-Butanol, the quencher of PLD, generated PA leading to the formation of physiologically inactive phosphatidyl butanol but not its biologically inactive analog, 2-butanol, blocked the H2O2-mediated barrier dysfunction. Furthermore, cell permeable C2 ceramide, an inhibitor of PLD but not the C2 dihydroceramide, attenuated the H2O2-induced PLD activation and enhancement of paracellular permeability of Evans blue conjugated albumin across the BPAEC monolayers. In addition, transfection of BPAECs with adenoviral constructs of hPLD1 and mPLD2 mutants attenuated the H2O2-induced barrier dysfunction, cytoskeletal reorganization and distribution of focal adhesion proteins. For the first time, this study demonstrated that the PLD-generated intracellular bioactive lipid signal mediator, PA, played a critical role in the ROS-induced barrier dysfunction in lung vascular ECs. This study also underscores the importance of PLD signaling in vascular leak and associated tissue injury in the etiology of lung diseases among critically ill patients encountering oxygen toxicity and excess ROS production during ventilator-assisted breathing.

  12. Mitochondrial Redox Signaling: Interaction of Mitochondrial Reactive Oxygen Species with Other Sources of Oxidative Stress

    OpenAIRE

    Schulz, Eberhard; Wenzel, Philip; Münzel, Thomas; Daiber, Andreas

    2014-01-01

    Significance: Oxidative stress is a well established hallmark of cardiovascular disease and there is strong evidence for a causal role of reactive oxygen and nitrogen species (RONS) therein. Recent Advances: Improvement of cardiovascular complications by genetic deletion of RONS producing enzymes and overexpression of RONS degrading enzymes proved the involvement of these species in cardiovascular disease at a molecular level. Vice versa, overexpression of RONS producing enzymes as well as de...

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

    OpenAIRE

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

    2014-01-01

    Fertilization and reproduction are central to the survival and propagation of a species. Couples who cannot reproduce naturally have to undergo in vitro clinical procedures. An integral part of these clinical procedures includes isolation of healthy sperm from raw semen. Existing sperm sorting methods are not efficient and isolate sperm having high DNA fragmentation and reactive oxygen species, and suffer from multiple manual steps and variations between embryologists. Inspired by in vivo nat...

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Mitochondrial reactive oxygen species (ROS) are widely implicated in physiological and pathological pathways. We propose that it is critical to understand the specific sites of mitochondrial ROS production and their mechanisms of action. Mitochondria possess at least eight distinct sites of ROS p...

  17. Transcriptomic footprints disclose specificity of reactive oxygen species signaling in Arabidopsis

    NARCIS (Netherlands)

    Gadjev, Ilya; Vanderauwera, Sandy; Gechev, Tsanko S.; Laloi, Christophe; Minkov, Ivan N.; Shulaev, Vladimir; Apel, Klaus; Inze, Dirk; Mittler, Ron; Van Breusegem, Frank

    2006-01-01

    Transcriptomic Footprints Disclose Specificity of Reactive Oxygen Species Signaling in Arabidopsis1,[W] Ilya Gadjev2, Sandy Vanderauwera2, Tsanko S. Gechev, Christophe Laloi, Ivan N. Minkov, Vladimir Shulaev, Klaus Apel, Dirk Inzé, Ron Mittler and Frank Van Breusegem* Department of Plant Systems Bio

  18. Live-cell assessment of mitochondrial reactive oxygen species using dihydroethidine

    NARCIS (Netherlands)

    Forkink, M.; Willems, P.H.; Koopman, W.J.H.; Grefte, Sander

    2015-01-01

    Reactive oxygen species (ROS) play an important role in both physiology and pathology. Mitochondria are an important source of the primary ROS superoxide. However, accurate detection of mitochondrial superoxide especially in living cells remains a difficult task. Here, we describe a method and the p

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

    Science.gov (United States)

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

  20. Associative oxygen species on the oxidized silver surface formed under O 2 microwave excitation

    Science.gov (United States)

    Boronin, A. I.; Koscheev, S. V.; Murzakhmetov, K. T.; Avdeev, V. I.; Zhidomirov, G. M.

    2000-09-01

    The experimental methods of X-ray and ultraviolet photoelectron spectroscopies (XPS and UPS, respectively) and the quantum mechanical calculations are applied for analysis of oxygen states on the silver oxide surface. At low temperatures ( Tozonide-like structures is preferable to that of peroxide species. Thermal stability and the reaction probability of the adsorbed states are investigated.

  1. Respiratory adaptations to oxygen lack in three species of Glossiphoniidae (Hirudinea) in Lake Esrom, Denmark

    DEFF Research Database (Denmark)

    Pohle, B. D.; Hamburger, K.

    2005-01-01

    The weight-specific respiration rate (µl O2 mg-1 AFDW h-1) of three species of leech from Lake Esrom, Denmark, Glossiphonia concolor, G. complanata and Helobdella stagnalis was measured in a closed stirred chamber with a micro electrode. At declining oxygen concentration (mg O2 l-1) all three...

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

    Science.gov (United States)

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

  3. Some Applications of Fast Neutron Activation Analysis of Oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Owrang, Farshid

    2003-07-01

    In this thesis we focus on applications of neutron activation of oxygen for several purposes: A) measuring the water level in a laboratory tank, B) measuring the water flow in a pipe system set-up, C) analysing the oxygen in combustion products formed in a modern gasoline SI engine, and D) measuring on-line the amount of oxygen in bulk liquids. A) Water level measurements. The purpose of this work was to perform radiation based water level measurements, aimed at nuclear reactor vessels, on a laboratory scale. A laboratory water tank was irradiated by fast neutrons from a neutron generator. The water was activated at different water levels and the water level was decreased. The produced gamma radiation was measured using two detectors at different heights. The results showed that the method is suitable for measurement of water level and that a relatively small experimental set-up can be used for developing methods for water level measurements in real boiling water reactors based on activated oxygen in the water. B) Water flows in pipe. The goal in this work was to investigate the asymmetric distribution of activity in flow measurements with pulsed neutron activation (PNA) in a laboratory piping system. Earlier investigations had shown a discrepancy between the measured velocity of the activated water by PNA and the true mean velocity in the pipe. This discrepancy decreased with larger distances from the activation point. It was speculated that the induced activity in the pipe did not distribute homogeneously. With inhomogeneous radial distribution of activity in combination with a velocity profile in the pipe, the activated water may not have the same velocity as the mean velocity of water in the pipe. To study this phenomenon, a water-soluble colour was injected into a transparent pipe for simulation of the transport of the activated water. The radial concentration of the colour, at different distances from the activation point, was determined. The result

  4. Robust DNA Damage Response and Elevated Reactive Oxygen Species in TINF2-Mutated Dyskeratosis Congenita Cells.

    Directory of Open Access Journals (Sweden)

    Larisa Pereboeva

    Full Text Available Dyskeratosis Congenita (DC is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF syndromes, converges on the DNA damage response (DDR pathway and subsequent elevation of reactive oxygen species (ROS. Historically, DC patients have had poor outcomes following bone marrow transplantation (BMT, perhaps as a consequence of an underlying DNA hypersensitivity to cytotoxic agents. Previously, we demonstrated an activated DDR and increased ROS, augmented by chemotherapy and radiation, in somatic cells isolated from DC patients with a mutation in the RNA component of telomerase, TERC. The current study was undertaken to determine whether previous findings related to ROS and DDR in TERC patients' cells could be extended to other DC mutations. Of particular interest was whether an antioxidant approach could counter increased ROS and decrease DC pathologies. To test this, we examined lymphocytes from DC patients from different DC mutations (TERT, TINF2, and TERC for the presence of an active DDR and increased ROS. All DC mutations led to increased steady-state p53 (2-fold to 10-fold and ROS (1.5-fold to 2-fold. Upon exposure to ionizing radiation (XRT, DC cells increased in both DDR and ROS to a significant degree. Exposing DC cells to hydrogen peroxide also revealed that DC cells maintain a significant oxidant burden compared to controls (1.5-fold to 3-fold. DC cell culture supplemented with N-acetylcysteine, or alternatively grown in low oxygen, afforded significant proliferative benefits (proliferation: maximum 2-fold increase; NAC: 5-fold p53 decrease; low oxygen: maximum 3.5-fold p53 decrease. Together, our data supports a

  5. Robust DNA Damage Response and Elevated Reactive Oxygen Species in TINF2-Mutated Dyskeratosis Congenita Cells.

    Science.gov (United States)

    Pereboeva, Larisa; Hubbard, Meredith; Goldman, Frederick D; Westin, Erik R

    2016-01-01

    Dyskeratosis Congenita (DC) is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF) syndromes, converges on the DNA damage response (DDR) pathway and subsequent elevation of reactive oxygen species (ROS). Historically, DC patients have had poor outcomes following bone marrow transplantation (BMT), perhaps as a consequence of an underlying DNA hypersensitivity to cytotoxic agents. Previously, we demonstrated an activated DDR and increased ROS, augmented by chemotherapy and radiation, in somatic cells isolated from DC patients with a mutation in the RNA component of telomerase, TERC. The current study was undertaken to determine whether previous findings related to ROS and DDR in TERC patients' cells could be extended to other DC mutations. Of particular interest was whether an antioxidant approach could counter increased ROS and decrease DC pathologies. To test this, we examined lymphocytes from DC patients from different DC mutations (TERT, TINF2, and TERC) for the presence of an active DDR and increased ROS. All DC mutations led to increased steady-state p53 (2-fold to 10-fold) and ROS (1.5-fold to 2-fold). Upon exposure to ionizing radiation (XRT), DC cells increased in both DDR and ROS to a significant degree. Exposing DC cells to hydrogen peroxide also revealed that DC cells maintain a significant oxidant burden compared to controls (1.5-fold to 3-fold). DC cell culture supplemented with N-acetylcysteine, or alternatively grown in low oxygen, afforded significant proliferative benefits (proliferation: maximum 2-fold increase; NAC: 5-fold p53 decrease; low oxygen: maximum 3.5-fold p53 decrease). Together, our data supports a mechanism

  6. Influence of Pretreatment on the Interaction of Oxygen with Silver and the Catalytic Activity of Ag/SiO2 Catalysts for CO Selective Oxidation in H2

    Institute of Scientific and Technical Information of China (English)

    Zhenping Qua; Mojie Cheng; Chuan Shi; Xinhe Bao

    2005-01-01

    The interactions of oxygen with pre-reduced silver catalysts as well as their catalytic properties for CO selective oxidation in H2 after oxygen pre-treatment are studied in this paper. It is found that the pretreatment exerts a strong influence on the activity and selectivity of the silver catalyst. A drop in activity and selectivity is observed after treating a pre-reduced catalyst with oxygen at low temperatures,whereas a converse result is obtained after an oxidizing treatment at high temperatures (T≥350 ℃). O2-TPD results show that surface oxygen species adsorbs on silver surface after the oxygen treatment at low temperatures. However, penetration of oxygen into the silver is enhanced by a high temperature treatment, meanwhile the surface oxygen species disappear. No other silver species except metallic silver are observed on all the catalysts by XRD, and the size of silver particle is not changed after the treatment with oxygen at low temperatures. The surface oxygen species formed by oxygen treatment can also be removed by hydrogen reduction. The strongly-adsorbed surface oxygen species prohibit the adsorption and diffusion of oxygen species in reaction gas on the surface of silver catalyst, causing the decrease in CO oxidation activity, in other words, it is important to obtain a clean silver surface for increasing the catalyst activity in CO removal from H2-rich feed gas. The differences in activity and selectivity due to the oxygen pretreatment at different temperatures are discussed in terms of the changes in the surface/subsurface oxygen species of the silver particles.

  7. Development of nitroxide radicals-containing polymer for scavenging reactive oxygen species from cigarette smoke

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2012-07-01

    In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase’s stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme’s exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a ‘sacrificial barrier’ by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO2 (100 ppm).

  9. Isoalantolactone Induces Reactive Oxygen Species Mediated Apoptosis in Pancreatic Carcinoma PANC-1 Cells

    Directory of Open Access Journals (Sweden)

    Muhammad Khan, Chuan Ding, Azhar Rasul, Fei Yi, Ting Li, Hongwen Gao, Rong Gao, Lili Zhong, Kun Zhang, Xuedong Fang, Tonghui Ma

    2012-01-01

    Full Text Available Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC, a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma.

  10. Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling.

    Science.gov (United States)

    Corcionivoschi, Nicolae; Alvarez, Luis A J; Sharp, Thomas H; Strengert, Monika; Alemka, Abofu; Mantell, Judith; Verkade, Paul; Knaus, Ulla G; Bourke, Billy

    2012-07-19

    Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling.

  11. Lycopene induces apoptosis in Candida albicans through reactive oxygen species production and mitochondrial dysfunction.

    Science.gov (United States)

    Choi, Hyemin; Lee, Dong Gun

    2015-08-01

    Lycopene, a well-known carotenoid pigment found in tomatoes, has shown various biological functions. In our previous report, we showed that lycopene induces two apoptotic hallmarks, plasma membrane depolarization and G2/M cell cycle arrest, in Candida albicans. In this study, we investigated the ability of lycopene to induce apoptosis, and the mechanism by which it regulates apoptosis. FITC-Annexin V staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, and 4',6-diamidino-2-phenylindole (DAPI) assay showed that lycopene exerted its antifungal activity during the early and late stages of apoptosis in C. albicans. During apoptosis, intracellular reactive oxygen species (ROS) were increased, and specifically the hydroxyl radicals contributed to the fungal cell death. Furthermore, lycopene treatment caused intracellular Ca(2+) overload and mitochondrial dysfunction, such as mitochondrial depolarization and cytochrome c release from the mitochondria to the cytoplasm. At last caspase activation was triggered. In summary, lycopene exerted its antifungal effects against C. albicans by inducing apoptosis via ROS production and mitochondrial dysfunction.

  12. Toxic effects of chlortetracycline on maize growth, reactive oxygen species generation and the antioxidant response

    Institute of Scientific and Technical Information of China (English)

    Bei Wen; Yu Liu; Peng Wang; Tong Wu; Shuzhen Zhang; Xiaoquan Shan; Jingfen Lu

    2012-01-01

    The toxicity of chlortetracycline (CTC) on maize (Zea mays L.) growth and reactive oxygen species (ROS) generation was studied.The root and shoot lengths and fresh weights of maize seedlings were inhibited by CTC treatment (p < 0.05).Root length was more sensitive than other parameters with the EC10 value of 0.064 mg/L.The spin trapping technique followed by electron paramagnetic resonance (EPR) analysis was used to quantify the ROS production.The ROS generated in maize roots after exposure to CTC was identified as hydroxyl radical (-OH).The EPR signal intensity correlated positively with the logarithm of CTC concentrations exposed (p < 0.05).The dynamic changes of malondialdehyde (MDA) contents and the antioxidative enzyme activities in maize roots were also determined.As compared to the control group,CTC was found to significantly increase MDA content.Treatment of maize roots with the ·OH scavenger sodium benzoate (SB) reduced the MDA content and enhanced the antioxidative enzyme activities.The results demonstrated the harmfulness of CTC at high dose to maize in the early developmental stage,and clarified that the inducement of ·OH is one of the mechanisms of CTC toxicity.

  13. Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Xinfeng Chen

    2016-01-01

    Full Text Available Reactive oxygen species (ROS produced by cellular metabolism play an important role as signaling messengers in immune system. ROS elevated in the tumor microenvironment are associated with tumor-induced immunosuppression. T cell-based therapy has been recently approved to be effective for cancer treatment. However, T cells often become dysfunctional after reaching the tumor site. It has been reported that ROS participate extensively in T cells activation, apoptosis, and hyporesponsiveness. The sensitivity of T cells to ROS varies among different subsets. ROS can be regulated by cytokines, amino acid metabolism, and enzymatic activity. Immunosuppressive cells accumulate in the tumor microenvironment and induce apoptosis and functional suppression of T cells by producing ROS. Thus, modulating the level of ROS may be important to prolong survival of T cells and enhance their antitumor function. Combining T cell-based therapy with antioxidant treatment such as administration of ROS scavenger should be considered as a promising strategy in cancer treatment, aiming to improve antitumor T cells immunity.

  14. Reactive oxygen species enhance TLR10 expression in the human monocytic cell line THP-1.

    Science.gov (United States)

    Kim, Donghee; Kim, Yeon Ju; Koh, Hyun Sook; Jang, Tae Yang; Park, Hyo Eun; Kim, Jae Young

    2010-01-01

    We investigated TLR10 expression in human monocytes, THP-1 cells, cultured in hypoxia (3% O(2)). Levels of both TLR10 mRNA and protein in THP-1 cells cultured in hypoxia were significantly higher than those cultured in normoxia (20% O(2)). We examined intracellular reactive oxygen species (ROS) content in hypoxic cells, and TLR10 expression in cells treated with hydrogen peroxide (H(2)O(2)), to determine whether the increase in TLR10 expression observed with hypoxia was due to an increase in intracellular ROS levels. We found that the level of intracellular ROS in cells subject to hypoxia was significantly higher than in normoxia. Experiments with ROS synthesis inhibitors revealed that hypoxia induced ROS production is mainly due to NADPH oxidase activity. TLR10 mRNA expression was increased by treatment with H(2)O(2) at concentrations ranging from 50 to 250 μM. We screened the TLR10 promoter and found putative binding sites for transcription factors (TFs), such as NF-κB, NF-AT and AP-1. Next, we examined TF activities using a luciferase reporter assay. Activities of NF-κB, NF-AT and AP-1 in the cells treated with H(2)O(2) were significantly higher than in untreated cells. The experiment with TF inhibitors revealed that ROS-induced upregulation of TLR10 expression is mainly due to NF-κB activation. Overall, our results suggest that hypoxia or ROS increase TLR10 expression in human monocytes and the transcriptional activities of NF-κB are involved in this process. Therefore, it is suggested that ROS produced by various exogenous stimuli may play a crucial role in the regulation of expression and function of TLR10 as second messengers.

  15. Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang-Hyun; Jang, Hae-Dong, E-mail: haedong@hnu.kr

    2015-02-15

    Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos–nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)–cSrc–phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. - Highlights: • Scoparone dose-dependently inhibited RANKL-induced osteoclast differentiation. • Scoparone diminished general ROS and superoxide anions in a dose-dependent manner. • Scoparone inhibited Nox1 expression and

  16. Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging

    International Nuclear Information System (INIS)

    Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos–nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)–cSrc–phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. - Highlights: • Scoparone dose-dependently inhibited RANKL-induced osteoclast differentiation. • Scoparone diminished general ROS and superoxide anions in a dose-dependent manner. • Scoparone inhibited Nox1 expression and

  17. Active oxygen and cell death in cereal aleurone cells.

    Science.gov (United States)

    Fath, Angelika; Bethke, Paul; Beligni, Veronica; Jones, Russell

    2002-05-01

    The cereal aleurone layer is a secretory tissue whose function is regulated by gibberellic acid (GA) and abscisic acid (ABA). Aleurone cells lack functional chloroplasts, thus excluding photosynthesis as a source of active oxygen species (AOS) in cell death. Incubation of barley aleurone layers or protoplasts in GA initiated the cell death programme, but incubation in ABA delays programmed cell death (PCD). Light, especially blue and UV-A light, and H(2)O(2) accelerate PCD of GA-treated aleurone cells, but ABA-treated aleurone cells are refractory to light and H(2)O(2) and are not killed. It was shown that light elevated intracellular H(2)O(2), and that the rise in H(2)O(2) was greater in GA-treated cells compared to cells in ABA. Experiments with antioxidants show that PCD in aleurone is probably regulated by AOS. The sensitivity of GA-treated aleurone to light and H(2)O(2) is a result of lowered amounts of enzymes that metabolize AOS. mRNAs encoding catalase, ascorbate peroxidase and superoxide dismutase are all reduced during 6-18 h of incubation in GA, but these mRNAs were present in higher amounts in cells incubated in ABA. The amounts of protein and enzyme activities encoded by these mRNAs were also dramatically reduced in GA-treated cells. Aleurone cells store and metabolize neutral lipids via the glyoxylate cycle in response to GA, and glyoxysomes are one potential source of AOS in the GA-treated cells. Mitochondria are another potential source of AOS in GA-treated cells. AOS generated by these organelles bring about membrane rupture and cell death.

  18. Reactive oxygen species and PI3K/Akt signaling in cancer.

    Science.gov (United States)

    Jin, Seo Yeon; Lee, Hye Sun; Kim, Eun Kyoung; Ha, Jung Min; Kim, Young Whan; Bae, SunSik

    2014-10-01

    Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen and associates with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In the present study, we showed that Insulin-like growth factor-1(IGF-1) modulates SKOV-3 ovarian cancer cell by regulation of generation of ROS. Akt mediates cellular signaling pathways in association with mammalian target of rapamycin complex (mTOR) and Rac small G protein. Insulin-like growth factor-1 (IGF-1)-induced generation of ROS was completely abolished by phosphatidylinositol 3-kinase (PI3K) (LY294002, 10?µM) or Akt inhibitors (SH-5, 50?µM), whereas inhibition of extracellular-regulated kinase by an ERK inhibitor (PD98059, 10?µM) or inhibition of mammalian target of rapamycin complex 1 (mTORC1) by an mTORC1 inhibitor (Rapamycin, 100?nM) did not affect IGF-1-induced generation of ROS. Inactivation of mTORC2 by silencing Rapamycin-insensitive companion of mTOR (Rictor), abolished IGF-1-induced SKOV-3 cell migration as well as activation of Akt. However, inactivation of mTORC1 by silencing of Raptor had no effect. Silencing of Akt1 but not Akt2 attenuated IGF-1-induced generation of ROS. Expression of PIP3-dependent Rac exchanger1 (P-Rex1), a Rac guanosine exchange factor and a component of the mTOR complex. Silencing of P-Rex1 abolished IGF-1-induced generation of ROS. Finally, inhibition of NADPH oxidase system completely blunted IGF-1-induced generation of ROS, whereas inhibition of xanthine oxiase,cyclooxygenase, and mitochondrial respiratory chain complex was not effective. Given these results, we suggest that IGF-1 induces ROS generation through the PI3K/Akt/ mTOR2/NADPH oxidase signaling axis. PMID:26461347

  19. Molecular Oxygen and Reactive Oxygen Species in Bread-making Processes: Scarce, but Nevertheless Important.

    Science.gov (United States)

    Decamps, Karolien; Joye, Iris J; De Vos, Dirk E; Courtin, Christophe M; Delcour, Jan A

    2016-01-01

    In bread making, O2 is consumed by flour constituents, yeast, and, optionally, some additives optimizing dough processing and/or product quality. It plays a major role especially in the oxidation/reduction phenomena in dough, impacting gluten network structure. The O2 level is about 7.2 mmol/kg dough, of which a significant part stems from wheat flour. We speculate that O2 is quickly lost to the atmosphere during flour hydration. Later, when the gluten network structure develops, some O2 is incorporated in dough through mixing-in of air. O2 is consumed by yeast respiration and in a number of reactions catalyzed by a wide range of enzymes present or added. About 60% of the O2 consumption in yeastless dough is ascribed to oxidation of fatty acids by wheat lipoxygenase activity. In yeasted dough, about 70% of the O2 in dough is consumed by yeast and wheat lipoxygenase. This would leave only about 30% for other reactions. The severe competition between endogenous (and added) O2-consuming systems impacts the gluten network. Moreover, the scarce literature data available suggest that exogenous oxidative enzymes but not those in flour may promote crosslinking of arabinoxylan in yeastless dough. In any case, dough turns anaerobic during the first minutes of fermentation. PMID:26055405

  20. [Studying the influence of some reactive oxygen species on physical and chemical parameters of blood].

    Science.gov (United States)

    Martusevich, A K; Martusevich, A A; Solov'eva, A G; Peretyagin, S P

    2014-01-01

    The aim of this work was to estimate the dynamics of blood physical and chemical parameters when blood specimens were processed by singlet oxygen in vitro. Our experiments were executed with whole blood specimens of healthy people (n=10). Each specimen was divided into five separate portions of 5 ml. The first portion was a control (without any exposures). The second one was processed by an oxygen-ozone mixture (at ozone concentration of 500 mcg/l, the third portion--by oxygen, and the fourth and fifth ones were processed by a gas mixture with singlet oxygen (50 and 100% of generator power). In blood samples after processing we studied the activity of lactate dehydrogenase, aldehyde dehydrogenase and superoxide dismutase, erythrocyte and plasma levels of glucose and lactate, acid-base balance and the partial pressure of gases in blood. It was found out, that blood processing by singlet oxygen leads to optimization of energy, detoxication and antioxidant enzymes functioning with changes in plasma and erythrocyte level of glucose and lactate, normalization of blood gases level and acid-base balance. Our results show, that the effect of singlet oxygen on enzyme activity is more pronounced than exposure to an oxygen-ozone gas mixture. PMID:25702489

  1. Induction of apoptosis by the plant alkaloid sampangine in human HL-60 leukemia cells is mediated by reactive oxygen species.

    Science.gov (United States)

    Kluza, Jérôme; Mazinghien, Romain; Degardin, Klara; Lansiaux, Amélie; Bailly, Christian

    2005-11-21

    Sampangine is a plant-derived copyrine alkaloid extracted from the stem bark of Cananga odorata. This azaoxoaporphine alkaloid primarily exhibits antifungal and antimycobacterial activities but also displays in vitro antimalarial activity against Plasmodium falciparum and it is cytotoxic to human malignant melanoma cells. Recently, sampangine was described as a pro-apoptotic agent, but the biochemical pathway leading to cell death remained unclear. Considering that sampangine possesses an iminoquinone moiety, potentially functioning as an oxidizing agent, we have investigated the implication of an oxidant stress on sampangine-induced cytotoxicity. We show that the treatment of human HL-60 leukemia cells for 48 h with sampangine induced an important oxidative burst. Real time flow cytometry measurements indicated that the production of oxidative species is very rapid, within minutes following the drug addition. Quenching of reactive oxygen species by the antioxidants N-acetyl cystein, vitamin C and vitamin E abolishes the pro-apoptotic activity of sampangine. The drug-induced production of reactive oxygen species is associated with cell cycle perturbations and mitochondrial alterations. This study shed light on the mechanism of action of sampangine and provides novel opportunities to use azaoxoaporphine alkaloids as lead compounds for the design of pro-apoptotic anticancer agents. PMID:16289142

  2. Reactive oxygen species metabolism during the cadmium hyperaccumulation of a new hyperaccumulator Sedum alfredii (Crassulaceae)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Sedum alfredii Hance, a newly discovered hyperaccumulator, could serve as a good material for phytoremediation Cd polluted sites. Malondialdehyde (MDA), reactive oxygen species (ROS) and antioxidases (catalase (CAT); superoxide dismutase (SOD); peroxidase (POD)) in the leaf were determined when S. alfredii was treated for 15 d with various CdCl2 concentrations ranging from 0 to 800 μmol/L. The results showed that the production rate of 2′,7′-dichlorofluorescein (DCF), which is an indicator of ROS level, reached up to the maximum at 400 μmol/L CdCl2 and then declined with the increase of CdCl2 concentration, while MDA accumulation tended to increase. CAT activity was significantly inhibited at all tested CdCl2 concentrations and SOD activity was sharply suppressed at 800 μmol/L CdCl2. However, the enhancement of POD activity was observed when CdCl2 concentration was higher than 400 μmol/L. In addition, its activity increased when treated with 600 μmol/L CdCl2 for more than 5 d. When sodium benzoate, a free radical scavenger, was added, S. alfredii was a little more sensitive to Cd toxicity than that exposed to Cd alone, and the Cd accumulation tended to decline with the increase of sodium benzoate concentration. It came to the conclusions that POD played an important role during Cd hyperaccumulation, and the accumulation of ROS induced by Cd treatment might be involved in Cd hyperaccumulation.

  3. Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen species generation.

    Science.gov (United States)

    Pfeiffer, Zachary A; Guerra, Alma N; Hill, Lindsay M; Gavala, Monica L; Prabhu, Usha; Aga, Mini; Hall, David J; Bertics, Paul J

    2007-05-15

    Macrophage activation is critical in the innate immune response and can be regulated by the nucleotide receptor P2X7. In this regard, P2X7 signaling is not well understood but has been implicated in controlling reactive oxygen species (ROS) generation by various leukocytes. Although ROS can contribute to microbial killing, the role of ROS in nucleotide-mediated cell signaling is unclear. In this study, we report that the P2X7 agonists ATP and 3'-O-(4-benzoyl) benzoic ATP (BzATP) stimulate ROS production by RAW 264.7 murine macrophages. These effects are potentiated in lipopolysaccharide-primed cells, demonstrating an important interaction between extracellular nucleotides and microbial products in ROS generation. In terms of nucleotide receptor specificity, RAW 264.7 macrophages that are deficient in P2X7 are greatly reduced in their capacity to generate ROS in response to BzATP treatment (both with and without LPS priming), thus supporting a role for P2X7 in this process. Because MAP kinase activation is key for nucleotide regulation of macrophage function, we also tested the hypothesis that P2X7-mediated MAP kinase activation is dependent on ROS production. We observed that BzATP stimulates MAP kinase (ERK1/ERK2, p38, and JNK1/JNK2) phosphorylation and that the antioxidants N-acetylcysteine and ascorbic acid strongly attenuate BzATP-mediated JNK1/JNK2 and p38 phosphorylation but only slightly reduce BzATP-induced ERK1/ERK2 phosphorylation. These studies reveal that P2X7 can contribute to macrophage ROS production, that this effect is potentiated upon lipopolysaccharide exposure, and that ROS are important participants in the extracellular nucleotide-mediated activation of several MAP kinase systems. PMID:17448897

  4. [Mast cells, their adenosine receptors and reactive oxygen species in chronic inflammatory pathologies of childhood].

    Science.gov (United States)

    Renke, Joanna; Popadiuk, Stefan; Wozniak, Michał; Szlagatys-Sidorkiewicz, Agnieszka; Hansdorfer-Korzon, Rita

    2006-01-01

    Mast cells were described by Erhlich at the end of XIX-th century. Their role was deeply investigated in asthma and allergy. The massive degranulation of mast cells in allergy can lead to anaphylactic shock. Recently, mast cells have been recognized again as a very interesting topic for investigation, due to their possible role in chronic inflammation. Moreover, through adenosine receptors, mast cells can be activated or inactivated. That is why these cells are regarded as a potential target of new drugs. It has been reported, that mast cells generate intracellular reactive oxygen species (ROS) in response to stimulation with divergent physiologically relevant stimulants. The intensification of ROS production may be measured by the level of carbonyl groups, as a marker of protein peroxidation. However, the role of mast cells in other than asthma diseases with chronic inflammation needs further investigation. It was found out that the information about mast cell distribution in colonic mucosa may serve as help in differentiation between inflammatory bowel disease and collagenous colitis. Moreover, its accumulation in focal active gastritis was confirmed in patients with Crohn's disease. An important role in regulation of inflammatory process seems to be reserved for adenosine receptors present on mastocytes. The activation of mast cells through the adenosine receptor is connected with 11-8 release, which stimulate the migration of leukocytes and oxidation reactions. The detection of mast cells in tissues should not be limited only to the simple histologic examination. It should be completed by the detection of products of degranulation, e.g. tryptase. This is the way to find out their actual function and state of activation. PMID:17203808

  5. Antioxidant enzymes regulate reactive oxygen species during pod elongation in Pisum sativum and Brassica chinensis.

    Science.gov (United States)

    Liu, Nan; Lin, Zhifang; Guan, Lanlan; Gaughan, Gerald; Lin, Guizhu

    2014-01-01

    Previous research has focused on the involvement of reactive oxygen species (ROS) in cell wall loosening and cell extension in plant vegetative growth, but few studies have investigated ROS functions specifically in plant reproductive organs. In this study, ROS levels and antioxidant enzyme activities were assessed in Pisum sativum and Brassica chinensis pods at five developmental stages. In juvenile pods, the high levels of O2.- and .OH indicates that they had functions in cell wall loosening and cell elongation. In later developmental stages, high levels of .OH were also related to increases in cell wall thickness in lignified tissues. Throughout pod development, most of the O2.- was detected on plasma membranes of parenchyma cells and outer epidermis cells of the mesocarp, while most of the H2O2 was detected on plasma membranes of most cells throughout the mesocarp. This suggests that these sites are presumably the locations of ROS generation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) apparently contributed to ROS accumulation in pod wall tissues. Furthermore, specifically SOD and POD were found to be associated with pod growth through the regulation of ROS generation and transformation. Throughout pod development, O2.- decreases were associated with increased SOD activity, while changes in H2O2 accumulation were associated with changes in CAT and POD activities. Additionally, high POD activity may contribute to the generation of(.)OH in the early development of pods. It is concluded that the ROS are produced in different sites of plasma membranes with the regulation of antioxidant enzymes, and that substantial ROS generation and accumulation are evident in cell elongation and cell wall loosening in pod wall cells. PMID:24503564

  6. Combined Treatment With Peroxisome Proliferator-Activated Receptor (PPAR) Gamma Ligands and Gamma Radiation Induces Apoptosis by PPARγ-Independent Up-Regulation of Reactive Oxygen Species-Induced Deoxyribonucleic Acid Damage Signals in Non-Small Cell Lung Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Jong; Im, Chang-Nim; Park, Seon Hwa [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Moon, Eun-Yi [Department of Bioscience and Biotechnology, Sejong University, Seoul (Korea, Republic of); Hong, Sung Hee, E-mail: gobrian@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-04-01

    Purpose: To investigate possible radiosensitizing activities of the well-known peroxisome proliferator-activated receptor (PPAR)γ ligand ciglitazone and novel PPARγ ligands CAY10415 and CAY10506 in non-small cell lung cancer (NSCLC) cells. Methods and Materials: Radiosensitivity was assessed using a clonogenic cell survival assay. To investigate the mechanism underlying PPARγ ligand-induced radiosensitization, the subdiploid cellular DNA fraction was analyzed by flow cytometry. Activation of the caspase pathway by combined PPARγ ligands and γ-radiation treatment was detected by immunoblot analysis. Reactive oxygen species (ROS) were measured using 2,7-dichlorodihydrofluorescein diacetate and flow cytometry. Results: The 3 PPARγ ligands induced cell death and ROS generation in a PPARγ-independent manner, enhanced γ-radiation–induced apoptosis and caspase-3–mediated poly (ADP-ribose) polymerase (PARP) cleavage in vitro. The combined PPARγ ligand/γ-radiation treatment triggered caspase-8 activation, and this initiator caspase played an important role in the combination-induced apoptosis. Peroxisome proliferator-activated receptor-γ ligands may enhance the γ-radiation-induced DNA damage response, possibly by increasing γ-H2AX expression. Moreover, the combination treatment significantly increased ROS generation, and the ROS scavenger N-acetylcysteine inhibited the combined treatment-induced ROS generation and apoptotic cell death. Conclusions: Taken together, these results indicated that the combined treatment of PPARγ ligands and γ-radiation synergistically induced DNA damage and apoptosis, which was regulated by ROS.

  7. Antifungal activity of five species of Polygala

    Directory of Open Access Journals (Sweden)

    Susana Johann

    2011-09-01

    Full Text Available Crude extracts and fractions of five species of Polygala - P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa - were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 µg/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 µg/mL and 250 µg/mL, respectively and C. gattii (both with MICs of 250 µg/mL. Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 µg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain.

  8. Study the effect of radiation in the generation of reactive oxygen species in bacteria

    International Nuclear Information System (INIS)

    Radiation is the energy in the form electromagnetic waves of particulate matter travelling in the air. There are two forms of electromagnetic radiation that are mutagenic; ionizing radiation and non-ionizing radiation. Ionizing radiation, such as X-rays or gamma radiation carries enough energy to remove electrons from molecules in a cell. When electrons are removed from molecules, ions, free radicals are formed. Free radicals can damage most other molecules in a cell, such as DNA or RNA, by oxidizing them. Non-ionizing radiation, such as ultraviolet (UV) light, exerts its mutagenic effect by exciting electrons in molecules. Out of them, ionizing radiation has more energy that why it can easily penetrate through the cell wall of the bacteria as well as endospores. Insides the cell, they proteolyses the water into hydrogen ion and hydroxide ion which leads to the generation of reactive oxygen species is a collective term that describes the chemical species that are formed upon incomplete reduction of oxygen and includes the superoxide anion (O2-), hydrogen peroxide (H2O2) and the hydroxyl radical (HO).UV generates H2O2 and O2- (Hall et al., 1994; Zhang et al., 2003) through NADPH oxidases, xanthine oxidases in bacteria. (Shin et al., 2008). Treatment with antioxidants can dampen the detrimental effects of radiation exposure. Cytoplasmic irradiation can result in damage to nuclear DNA, and experiments with free radical scavengers have shown this DNA damage is dependent on ROS generation. As the result of irradiation, cells can produce ROS for several minutes or even hours after being exposed. In addition to ROS production, cells are stimulated to increase their expression of antioxidants. In response to ionizing radiation exposure, several signal transduction pathways (e.g., ERK1/2, JNK, p38, and ATM) and transcription factors (e.g., AP1, NFêB, GADD153, and p53) are activated. Many of these signalling and gene expression pathways are sensitive to changes in

  9. Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1

    Science.gov (United States)

    Chen, Yueqi; Sun, Jingjing; Dou, Ce; Li, Nan; Kang, Fei; Wang, Yuan; Cao, Zhen; Yang, Xiaochao; Dong, Shiwu

    2016-01-01

    The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated osteoclast-mediated bone resorption. It is reported that monocytes/macrophage progenitor cells or either hematopoietic stem cells (HSCs) gave rise to multinucleated osteoclasts. Thus, inhibition of osteoclastic bone resorption generally seems to be a predominant therapy for treating osteoporosis. Recently, more and more natural compounds have been discovered, which have the ability of inhibiting osteoclast differentiation and fusion. Alliin (S-allyl-l-cysteine sulfoxides, SACSO) is the major component of aged garlic extract (AGE), bearing broad-spectrum natural antioxidant properties. However, its effects on bone health have not yet been explored. Hence, we designed the current study to explore its effects and role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast fusion and differentiation. It was revealed that alliin had an inhibitory effect in osteoclasteogenesis with a dose-dependent manner via blocking the c-Fos-NFATc1 signaling pathway. In addition, alliin decreased the generation of reactive oxygen species (ROS) and down-regulated the expression of NADPH oxidase 1 (Nox1). The overall results revealed that alliin could be a potential therapeutic agent in the treatment of osteoporosis. PMID:27657047

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

    Science.gov (United States)

    Coughlan, Melinda T; Sharma, Kumar

    2016-08-01

    The paradigm that high glucose drives overproduction of superoxide from mitochondria as a unifying theory to explain end organ damage in diabetes complications has been tightly held for more than a decade. With the recent development of techniques and probes to measure the production of distinct reactive oxygen species (ROS) in vivo, this widely held dogma is now being challenged with the emerging view that specific ROS moieties are essential for the function of specific intracellular signaling pathways and represent normal mitochondrial function. This review will provide a balanced overview of the dual nature of ROS, detailing current evidence for ROS overproduction in diabetic kidney disease, with a focus on cell types and sources of ROS. The technical aspects of measurement of mitochondrial ROS, both in isolated mitochondria and emerging in vivo methods will be discussed. The counterargument, that mitochondrial ROS production is reduced in diabetic complications, is consistent with a growing recognition that stimulation of mitochondrial biogenesis and oxidative phosphorylation activity reduces inflammation and fibrosis. It is clear that there is an urgent need to fully characterize ROS production paying particular attention to spatiotemporal aspects and to factor in the relevance of ROS in the regulation of cellular signaling in the pathogenesis of diabetic kidney disease. With improved tools and real-time imaging capacity, a greater understanding of the complex role of ROS will be able to guide novel therapeutic regimens. PMID:27217197

  11. The Role of Reactive Oxygen Species in Myelofibrosis and Related Neoplasms

    Directory of Open Access Journals (Sweden)

    Mads Emil Bjørn

    2015-01-01

    Full Text Available Reactive oxygen species (ROS have been implicated in a wide variety of disorders ranging between traumatic, infectious, inflammatory, and malignant diseases. ROS are involved in inflammation-induced oxidative damage to cellular components including regulatory proteins and DNA. Furthermore, ROS have a major role in carcinogenesis and disease progression in the myeloproliferative neoplasms (MPNs, where the malignant clone itself produces excess of ROS thereby creating a vicious self-perpetuating circle in which ROS activate proinflammatory pathways (NF-κB which in turn create more ROS. Targeting ROS may be a therapeutic option, which could possibly prevent genomic instability and ultimately myelofibrotic and leukemic transformation. In regard to the potent efficacy of the ROS-scavenger N-acetyl-cysteine (NAC in decreasing ROS levels, it is intriguing to consider if NAC treatment might benefit patients with MPN. The encouraging results from studies in cystic fibrosis, systemic lupus erythematosus, and chronic obstructive pulmonary disease warrant such studies. In addition, the antioxidative potential of the widely used agents, interferon-alpha2, statins, and JAK inhibitors, should be investigated as well. A combinatorial approach using old agents with anticancer properties together with novel JAK1/2 inhibitors may open a new era for patients with MPNs, the outlook not only being “minimal residual disease” and potential cure but also a marked improvement in inflammation-mediated comorbidities.

  12. Reactive Oxygen Species as Additional Determinants for Cytotoxicity of Clostridium difficile Toxins A and B

    Science.gov (United States)

    Frädrich, Claudia; Beer, Lara-Antonia; Gerhard, Ralf

    2016-01-01

    Clostridium difficile infections can induce mild to severe diarrhoea and the often associated characteristic pseudomembranous colitis. Two protein toxins, the large glucosyltransferases TcdA and TcdB, are the main pathogenicity factors that can induce all clinical symptoms in animal models. The classical molecular mode of action of these homologous toxins is the inhibition of Rho GTPases by mono-glucosylation. Rho-inhibition leads to breakdown of the actin cytoskeleton, induces stress-activated and pro-inflammatory signaling and eventually results in apoptosis of the affected cells. An increasing number of reports, however, have documented further qualities of TcdA and TcdB, including the production of reactive oxygen species (ROS) by target cells. This review summarizes observations dealing with the production of ROS induced by TcdA and TcdB, dissects pathways that contribute to this phenomenon and speculates about ROS in mediating pathogenesis. In conclusion, ROS have to be considered as a discrete, glucosyltransferase-independent quality of at least TcdB, triggered by different mechanisms. PMID:26797634

  13. Reactive Oxygen Species as Additional Determinants for Cytotoxicity of Clostridium difficile Toxins A and B.

    Science.gov (United States)

    Frädrich, Claudia; Beer, Lara-Antonia; Gerhard, Ralf

    2016-01-01

    Clostridium difficile infections can induce mild to severe diarrhoea and the often associated characteristic pseudomembranous colitis. Two protein toxins, the large glucosyltransferases TcdA and TcdB, are the main pathogenicity factors that can induce all clinical symptoms in animal models. The classical molecular mode of action of these homologous toxins is the inhibition of Rho GTPases by mono-glucosylation. Rho-inhibition leads to breakdown of the actin cytoskeleton, induces stress-activated and pro-inflammatory signaling and eventually results in apoptosis of the affected cells. An increasing number of reports, however, have documented further qualities of TcdA and TcdB, including the production of reactive oxygen species (ROS) by target cells. This review summarizes observations dealing with the production of ROS induced by TcdA and TcdB, dissects pathways that contribute to this phenomenon and speculates about ROS in mediating pathogenesis. In conclusion, ROS have to be considered as a discrete, glucosyltransferase-independent quality of at least TcdB, triggered by different mechanisms. PMID:26797634

  14. Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading.

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    Morikawa, Daichi; Nojiri, Hidetoshi; Saita, Yoshitomo; Kobayashi, Keiji; Watanabe, Kenji; Ozawa, Yusuke; Koike, Masato; Asou, Yoshinori; Takaku, Tomoiku; Kaneko, Kazuo; Shimizu, Takahiko

    2013-11-01

    Oxidative stress contributes to the pathogenesis of age-related diseases as well as bone fragility. Our previous study demonstrated that copper/zinc superoxide dismutase (Sod1)-deficient mice exhibit the induction of intracellular reactive oxygen species (ROS) and bone fragility resulting from low-turnover bone loss and impaired collagen cross-linking (Nojiri et al. J Bone Miner Res. 2011;26:2682-94). Mechanical stress also plays an important role in the maintenance of homeostasis in bone tissue. However, the molecular links between oxidative and mechanical stresses in bone tissue have not been fully elucidated. We herein report that mechanical unloading significantly increased intracellular ROS production and the specific upregulation of Sod1 in bone tissue in a tail-suspension experiment. We also reveal that Sod1 loss exacerbated bone loss via reduced osteoblastic abilities during mechanical unloading. Interestingly, we found that the administration of an antioxidant, vitamin C, significantly attenuated bone loss during unloading. These results indicate that mechanical unloading, in part, regulates bone mass via intracellular ROS generation and the Sod1 expression, suggesting that activating Sod1 may be a preventive strategy for ameliorating mechanical unloading-induced bone loss.

  15. Mitochondrial physiology and reactive oxygen species production are altered by hypoxia acclimation in killifish (Fundulus heteroclitus).

    Science.gov (United States)

    Du, Sherry N N; Mahalingam, Sajeni; Borowiec, Brittney G; Scott, Graham R

    2016-04-15

    Many fish encounter hypoxia in their native environment, but the role of mitochondrial physiology in hypoxia acclimation and hypoxia tolerance is poorly understood. We investigated the effects of hypoxia acclimation on mitochondrial respiration, O2kinetics, emission of reactive oxygen species (ROS), and antioxidant capacity in the estuarine killifish ( ITALIC! Fundulus heteroclitus). Killifish were acclimated to normoxia, constant hypoxia (5 kPa O2) or intermittent diel cycles of nocturnal hypoxia (12 h:12 h normoxia:hypoxia) for 28-33 days and mitochondria were isolated from liver. Neither pattern of hypoxia acclimation affected the respiratory capacities for oxidative phosphorylation or electron transport, leak respiration, coupling control or phosphorylation efficiency. Hypoxia acclimation also had no effect on mitochondrial O2kinetics, but ITALIC! P50(the O2tension at which hypoxia inhibits respiration by 50%) was lower in the leak state than during maximal respiration, and killifish mitochondria endured anoxia-reoxygenation without any impact on mitochondrial respiration. However, both patterns of hypoxia acclimation reduced the rate of ROS emission from mitochondria when compared at a common O2tension. Hypoxia acclimation also increased the levels of protein carbonyls and the activities of superoxide dismutase and catalase in liver tissue (the latter only occurred in constant hypoxia). Our results suggest that hypoxia acclimation is associated with changes in mitochondrial physiology that decrease ROS production and may help improve hypoxia tolerance. PMID:26896545

  16. Cryptococcus neoformans capsule protects cell from oxygen reactive species generated by antimicrobial photodynamic inactivation

    Science.gov (United States)

    Prates, Renato Araujo; Hamblin, Michael R.; Kato, Ilka T.; Fuchs, Beth; Mylonakis, Eleytherios; Simões Ribeiro, Martha; Tegos, George

    2011-03-01

    Antimicrobial photodynamic inactivation (APDI) is based on the utilization of substances that can photosensitize biological tissues and are capable of being activated in the presence of light. Cryptococcus neoformans is an yeast surrounded by a capsule composed primarily of glucoronoxylomannan that plays an important role in its virulence. This yeast causes infection on skin, lungs and brain that can be associated with neurological sequelae and neurosurgical interventions, and its conventional treatment requires prolonged antifungal therapy, which presents important adverse effects. The aim of this study was to evaluate the protective effect of Cryptococcus neoformans capsule against reactive oxygen species generated by APDI. Cryptococcus neoformans KN99α, which is a strain able to produce capsule, and CAP59 that does not present capsule production were submitted to APDI using methylene blue (MB), rose bengal (RB), and pL-ce6 as photosensitizers (PS). Then microbial inactivation was evaluated by counting colony form units following APDI and confocal laser scanning microscopy (CLSM) illustrated localization as well as the preferential accumulation of PS into the fungal cells. C. neoformans KN99α was more resistant to APDI than CAP59 for all PSs tested. CLSM showed incorporation of MB and RB into the cytoplasm and a preferential uptake in mitochondria. A nuclear accumulation of MB was also observed. Contrarily, pL-ce6 appears accumulated in cell wall and cell membrane and minimal florescence was observed inside the fungal cells. In conclusion, the ability of C. neoformans to form capsule enhances survival following APDI.

  17. Arabidopsis CAP1-mediated ammonium sensing required reactive oxygen species in plant cell growth.

    Science.gov (United States)

    Bai, Ling; Zhou, Yun; Ma, Xiaonan; Gao, Lijie; Song, Chun-Peng

    2014-06-18

    [Ca (2+)]cyt-associated protein kinase (CAP) gene 1 is a receptor-like kinase that belongs to CrRLK1L (Catharanthus roseus Receptor like kinase) subfamily. CAP1 has been identified as a novel modulator of NH 4(+) in the tonoplast, which regulates root hair growth by maintaining the cytoplasmic Ca (2+) gradients. Different expression pattern of tonoplast intrinsic protein (TIP2;3) in the CAP1 knock out mutant and wild type on Murashige and Skoog (MS) medium suggested that CAP1 influences transport activity to regulate the compartmentalization of NH 4(+) into vacuole. Lower expression level of Oxidative Signal-Inducible1(OXI1) in the cap1-1 root and the abnormal reactive oxygen species (ROS) gradient in root hair of cap1-1 on MS medium indicated that ROS signaling involve in CAP1-regulated root hair growth. Wild-type-like ROS distribution pattern in the cap1-1 root hair can be reestablished in seedlings grown on NH 4(+) deficient medium, which indicated that CAP1 functions as a sensor for NH 4(+) signaling in maintaining tip-focused ROS gradient in root hairs polar growth. PMID:24940875

  18. Reactive oxygen species in paraventricular nucleus involved in cardiac sympathetic afferent reflex in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Zhang; Yang Yu; Ying Zhang; Yingchun Li; Luqing Zhang; Lingling Fan; Yingya Gao; Guoqing Zhu

    2005-01-01

    Objective: The present study was designed to determine if reactive oxygen species (ROS) in the paraventricularnucleus (PVN) were involved in modulating cardiac sympathetic afferent reflex (CSAR) in anesthetized rats. Methods: Malondialdehyde(MDA), the end product of lipid peroxidation, in the PVN, was determined by thiobarbituric acid (TBA) spectrometric method. Renalsympathetic nerve activity (RSNA) and arterial pressure were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSARwas evaluated by the response of the RSNA evoked by epicardial application of bradykinin (BK, 0.4 μg). Results: The MDA in the PVNwas significantly increased after epicardial application of BK compared with control (2.0 + 0.3 vs 0.8 + 0.1 nmol/mg protein, P < 0.01 ).Microinjectionof a superoxide anion scavenger, tiron (20 nmol) into the PVN significantly inhibited the CSAR evoked by BK (12.3 ± 1.9vs 4.2+ 1.2%, P < 0.01) and decreased MDA level (1.9±0.3 vs 0.6+0.1 nmol/mg protein, P <0.01) compared with control.Conclusion: The ROS in the PVN is involved in modulating the CSAR in rats.

  19. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function

    Directory of Open Access Journals (Sweden)

    Dylan Burger

    2016-01-01

    Full Text Available Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2∙- generation, and nitric oxide (NO production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47phox, p67phox, and p22phox and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2∙- production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation.

  20. Catalase eliminates reactive oxygen species and influences the intestinal microbiota of shrimp.

    Science.gov (United States)

    Yang, Hui-Ting; Yang, Ming-Chong; Sun, Jie-Jie; Guo, Fang; Lan, Jiang-Feng; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing

    2015-11-01

    Intestinal innate immune response is an important defense mechanism of animals and humans against external pathogens. The mechanism of microbiota homeostasis in host intestines has been well studied in mammals and Drosophila. The reactive oxygen species (ROS) and antimicrobial peptides have been reported to play important roles in homeostasis. However, how to maintain the microbiota homeostasis in crustacean intestine needs to be elucidated. In this study, we identified a novel catalase (MjCAT) involved in ROS elimination in kuruma shrimp, Marsupenaeus japonicus. MjCAT mRNA was widely distributed in hemocytes, heart, hepatopancreas, gills, stomach, and intestine. After the shrimp were challenged with pathogenic bacteria via oral infection, the expression level of MjCAT was upregulated, and the enzyme activity was increased in the intestine. ROS level was also increased in the intestine at early time after oral infection and recovered rapidly. When MjCAT was knocked down by RNA interference (RNAi), high ROS level maintained longer time, and the number of bacteria number was declined in the shrimp intestinal lumen than those in the control group, but the survival rate of the MjCAT-RNAi shrimp was declined. Further study demonstrated that the intestinal villi protruded from epithelial lining of the intestinal wall were damaged by the high ROS level in MjCAT-knockdown shrimp. These results suggested that MjCAT participated in the intestinal host-microbe homeostasis by regulating ROS level.

  1. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function.

    Science.gov (United States)

    Burger, Dylan; Turner, Maddison; Munkonda, Mercedes N; Touyz, Rhian M

    2016-01-01

    Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs) and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS) and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion (O2 (∙-)) generation, and nitric oxide (NO) production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p47(phox), p67(phox), and p22(phox) and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased O2 (∙-) production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation. PMID:27313830

  2. Impaired ADP channeling to mitochondria and elevated reactive oxygen species in hypertensive hearts.

    Science.gov (United States)

    Power, Amelia S C; Pham, Toan; Loiselle, Denis S; Crossman, David H; Ward, Marie-Louise; Hickey, Anthony J

    2016-06-01

    Systemic hypertension initially promotes a compensatory cardiac hypertrophy, yet it progresses to heart failure (HF), and energetic deficits appear to be central to this failure. However, the transfer of energy between the mitochondria and the myofibrils is not often considered as part of the energetic equation. We compared hearts from old spontaneously hypertensive rats (SHRs) and normotensive Wistar controls. SHR hearts showed a 35% depression in mitochondrial function, yet produced at least double the amount of reactive oxygen species (ROS) in all respiration states in left ventricular (LV) homogenates. To test the connectivity between mitochondria and myofibrils, respiration was further tested in situ with LV permeabilized fibers by addition of multiple substrates and ATP, which requires hydrolysis to mediate oxidative phosphorylation. By trapping ADP using a pyruvate kinase enzyme system, we tested ADP channeling towards mitochondria, and this suppressed respiration and elevated ROS production more in the SHR fibers. The ADP-trapped state was also less relieved on creatine addition, likely reflecting the 30% depression in total CK activity in the SHR heart fibers. Confocal imaging identified a 34% longer distance between the centers of myofibril to mitochondria in the SHR hearts, which increases transverse metabolite diffusion distances (e.g., for ATP, ADP, and creatine phosphate). We propose that impaired connectivity between mitochondria and myofibrils may contribute to elevated ROS production. Impaired energy exchange could be the result of ultrastructural changes that occur with hypertrophy in this model of hypertension. PMID:27084386

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

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    David Freeman

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

  4. Dental resin curing blue light induced oxidative stress with reactive oxygen species production.

    Science.gov (United States)

    Yoshino, Fumihiko; Yoshida, Ayaka; Okada, Eizo; Okada, Yasue; Maehata, Yojiro; Miyamoto, Chihiro; Kishimoto, Sachi; Otsuka, Takero; Nishimura, Tomoko; Lee, Masaichi Chang-il

    2012-09-01

    Dental resin curing blue light has been used in the treatment of tooth bleaching and to restore teeth with resin-based composite fillings. However, there has been little consideration of its effect on oral tissues such as dental pulp and oral mucosa. The aim of this study was to investigate whether dental resin curing blue light irradiation affects the dental pulp, especially the blood vessels that are known as the first target of reactive oxygen species (ROS), which play an important role in vascular reactivity. We found that blue light irradiation increased the level of lipid peroxidation in isolated rat aorta blood vessels by measuring malondialdehyde. Furthermore, cell proliferative activity was decreased in a time-dependent manner and apoptosis of human aorta vascular smooth muscle cells (VSMCs) was induced. These results indicated that (ROS) such as hydrogen peroxide and hydroxyl radicals were generated in VSMCs by irradiation with blue light, and they induced cytotoxicity associated with oxidative stress, which increased lipid peroxidation and apoptosis. In addition, N-acetyl-l-cysteine, which is a typical intracellular antioxidant, protected VSMCs against cytotoxicity associated with oxidative stress. These findings suggested that antioxidants may be used to prevent oxidative stress in dental pulp by repeated and/or multiple treatments with blue light irradiation in future dental treatments.

  5. Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species.

    Science.gov (United States)

    Shen, Fengge; Tang, Xudong; Cheng, Wei; Wang, Yang; Wang, Chao; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Liu, Mingyuan; Liu, Bo; Yu, Lu

    2016-01-01

    The successful treatment of bacterial infections is the achievement of a synergy between the host's immune defences and antibiotics. Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes, and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host's immune defences and antibiotic interactions in microbial infections. PMID:26778774

  6. Survival signaling by C-RAF: mitochondrial reactive oxygen species and Ca2+ are critical targets.

    Science.gov (United States)

    Kuznetsov, Andrey V; Smigelskaite, Julija; Doblander, Christine; Janakiraman, Manickam; Hermann, Martin; Wurm, Martin; Scheidl, Stefan F; Sucher, Robert; Deutschmann, Andrea; Troppmair, Jakob

    2008-04-01

    Survival signaling by RAF occurs through largely unknown mechanisms. Here we provide evidence for the first time that RAF controls cell survival by maintaining permissive levels of mitochondrial reactive oxygen species (ROS) and Ca(2+). Interleukin-3 (IL-3) withdrawal from 32D cells resulted in ROS production, which was suppressed by activated C-RAF. Oncogenic C-RAF decreased the percentage of apoptotic cells following treatment with staurosporine or the oxidative stress-inducing agent tert-butyl hydroperoxide. However, it was also the case that in parental 32D cells growing in the presence of IL-3, inhibition of RAF signaling resulted in elevated mitochondrial ROS and Ca(2+) levels. Cell death is preceded by a ROS-dependent increase in mitochondrial Ca(2+), which was absent from cells expressing transforming C-RAF. Prevention of mitochondrial Ca(2+) overload after IL-3 deprivation increased cell viability. MEK was essential for the mitochondrial effects of RAF. In summary, our data show that survival control by C-RAF involves controlling ROS production, which otherwise perturbs mitochondrial Ca(2+) homeostasis. PMID:18212057

  7. Vitamin D, reactive oxygen species and calcium signalling in ageing and disease.

    Science.gov (United States)

    Berridge, Michael J

    2016-08-01

    Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca(2+) and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca(2+) and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer's disease (AD). In cardiac cells, this deficiency alters the Ca(2+) transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca(2+) landscape that initiates amyloid formation, which then elevates the resting level of Ca(2+) to drive the memory loss that progresses to neuronal cell death and dementia.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377727

  8. Reactive oxygen species and angiotensin II signaling in vascular cells: implications in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Touyz R.M.

    2004-01-01

    Full Text Available Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.

  9. The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction.

    Science.gov (United States)

    Castro, José Pedro; Grune, Tilman; Speckmann, Bodo

    2016-08-01

    White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance. PMID:27031218

  10. Oleoyl-lysophosphatidylcholine limits endothelial nitric oxide bioavailability by induction of reactive oxygen species.

    Directory of Open Access Journals (Sweden)

    Andrijana Kozina

    Full Text Available Previously we reported modulation of endothelial prostacyclin and interleukin-8 production, cyclooxygenase-2 expression and vasorelaxation by oleoyl- lysophosphatidylcholine (LPC 18:1. In the present study, we examined the impact of this LPC on nitric oxide (NO bioavailability in vascular endothelial EA.hy926 cells. Basal NO formation in these cells was decreased by LPC 18:1. This was accompanied with a partial disruption of the active endothelial nitric oxide synthase (eNOS- dimer, leading to eNOS uncoupling and increased formation of reactive oxygen species (ROS. The LPC 18:1-induced ROS formation was attenuated by the superoxide scavenger Tiron, as well as by the pharmacological inhibitors of eNOS, NADPH oxidases, flavin-containing enzymes and superoxide dismutase (SOD. Intracellular ROS-formation was most prominent in mitochondria, less pronounced in cytosol and undetectable in endoplasmic reticulum. Importantly, Tiron completely prevented the LPC 18:1-induced decrease in NO bioavailability in EA.hy926 cells. The importance of the discovered findings for more in vivo like situations was analyzed by organ bath experiments in mouse aortic rings. LPC 18:1 attenuated the acetylcholine-induced, endothelium dependent vasorelaxation and massively decreased NO bioavailability. We conclude that LPC 18:1 induces eNOS uncoupling and unspecific superoxide production. This results in NO scavenging by ROS, a limited endothelial NO bioavailability and impaired vascular function.

  11. The stimulated innate resistance event in Bordetella pertussis infection is dependent on reactive oxygen species production.

    Science.gov (United States)

    Zurita, E; Moreno, G; Errea, A; Ormazabal, M; Rumbo, M; Hozbor, D

    2013-07-01

    The exacerbated induction of innate immune responses in airways can abrogate diverse lung infections by a phenomenon known as stimulated innate resistance (StIR). We recently demonstrated that the enhancement of innate response activation can efficiently impair Bordetella pertussis colonization in a Toll-like receptor 4 (TLR4)-dependent manner. The aim of this work was to further characterize the effect of lipopolysaccharide (LPS) on StIR and to identify the mechanisms that mediate this process. Our results showed that bacterial infection was completely abrogated in treated mice when the LPS of B. pertussis (1 μg) was added before (48 h or 24 h), after (24 h), or simultaneously with the B. pertussis challenge (10(7) CFU). Moreover, we detected that LPS completely cleared bacterial infection as soon as 2 h posttreatment. This timing suggests that the observed StIR phenomenon should be mediated by fast-acting antimicrobial mechanisms. Although neutrophil recruitment was already evident at this time point, depletion assays using an anti-GR1 antibody showed that B. pertussis clearance was achieved even in the absence of neutrophils. To evaluate the possible role of free radicals in StIR, we performed animal assays using the antioxidant N-acetyl cysteine (NAC), which is known to inactivate oxidant species. NAC administration blocked the B. pertussis clearance induced by LPS. Nitrite concentrations were also increased in the LPS-treated mice; however, the inhibition of nitric oxide synthetases did not suppress the LPS-induced bacterial clearance. Taken together, our results show that reactive oxygen species (ROS) play an essential role in the TLR4-dependent innate clearance of B. pertussis.

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

    Science.gov (United States)

    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, phorbol-12-Myristate-13-Acetate (PMA) increased the expression of specific OL differentiation markers: the specific nuclear factor Olig-2, and Myelin Basic Protein (MBP), which was processed and accumulated selectively in membranes. The induction of differentiation genes was associated with the activation of ERK1-2 and phosphorylation of the nuclear cAMP responsive element binding protein 1 (CREB). PKC mediates ROS-induced differentiation because PKC depletion or bis-indolyl-maleimide (BIM), a PKC inhibitor, reversed the induction of differentiation markers by H2O2. H2O2 and PMA increased the expression of membrane-bound NADPH oxidases, NOX3 and NOX5. Selective depletion of these proteins inhibited differentiation induced by PMA. Furthermore, NOX5 silencing down regulated NOX3 mRNA levels, suggesting that ROS produced by NOX5 up-regulate NOX3 expression. These data unravel an elaborate network of ROS-generating enzymes (NOX5 to NOX3) activated by PKC and necessary for differentiation of OLs. Furthermore, NOX3 and NOX5, as inducers of OL differentiation, represent novel targets for therapies of demyelinating diseases, including multiple sclerosis, associated with impairment of OL differentiation. PMID:27313511

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

    Science.gov (United States)

    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, phorbol-12-Myristate-13-Acetate (PMA) increased the expression of specific OL differentiation markers: the specific nuclear factor Olig-2, and Myelin Basic Protein (MBP), which was processed and accumulated selectively in membranes. The induction of differentiation genes was associated with the activation of ERK1-2 and phosphorylation of the nuclear cAMP responsive element binding protein 1 (CREB). PKC mediates ROS-induced differentiation because PKC depletion or bis-indolyl-maleimide (BIM), a PKC inhibitor, reversed the induction of differentiation markers by H2O2. H2O2 and PMA increased the expression of membrane-bound NADPH oxidases, NOX3 and NOX5. Selective depletion of these proteins inhibited differentiation induced by PMA. Furthermore, NOX5 silencing down regulated NOX3 mRNA levels, suggesting that ROS produced by NOX5 up-regulate NOX3 expression. These data unravel an elaborate network of ROS-generating enzymes (NOX5 to NOX3) activated by PKC and necessary for differentiation of OLs. Furthermore, NOX3 and NOX5, as inducers of OL differentiation, represent novel targets for therapies of demyelinating diseases, including multiple sclerosis, associated with impairment of OL differentiation. PMID:27313511

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

    Science.gov (United States)

    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′-tetramethyl-benzidine (TMB), as well as, analyzed the cytotoxic properties of PdNC on HeLa cells. Our findings showed no evidence of singlet oxygen production by PdNC. The nanocubes’ activity is not necessarily linked to activation of oxygen. The oxidation of substrate on PdNC can be a first step followed by PdNC regeneration with oxygen or other oxidant. The catalytic activity of PdNC towards oxidation of TMB is very high and shows direct two-electrons oxidation when the surface of PdNC is clean and the ratio of TMB/PdNC is not very high. Sequential one electron oxidation is observed when the pristine quality of PdNC surface is compromised by serum or uncontrolled impurities and/or the ratio of TMB/PdNC is high. Clean PdNC in serum-free media efficiently induce apoptosis of HeLa cells. It is the primary route of cell death and is associated with hyperpolarization of mitochondria, contrary to a common mitochondrial depolarization initiated by ROS. Again, the effects are very sensitive to how well the pristine surface of PdNC is preserved, suggesting that PdNC can be used as an apoptosis inducing agent but only with appropriate drug delivery system. PMID:25886644

  15. Evaluation of the catalytic activity and cytotoxicity of palladium nanocubes: the role of oxygen.

    Science.gov (United States)

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

    2015-05-13

    Recently, it has been reported that palladium nanocubes (PdNC) are capable of generating singlet oxygen without photoexcitation 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 3,3',5,5'-tetramethylbenzidine (TMB), and analyzed the cytotoxic properties of PdNC on HeLa cells. Our findings showed no evidence of singlet oxygen production by PdNC. The nanocubes' activity is not necessarily linked to activation of oxygen. The oxidation of substrate on PdNC can be a first step, followed by PdNC regeneration with oxygen or other oxidant. The catalytic activity of PdNC toward the oxidation of TMB is very high and shows direct two-electron oxidation when the surface of the PdNC is clean and the ratio of TMB/PdNC is not very high. Sequential one electron oxidation is observed when the pristine quality of PdNC surface is compromised by serum or uncontrolled impurities and/or the ratio of TMB/PdNC is high. Clean PdNC in serum-free media efficiently induce apoptosis of HeLa cells. It is the primary route of cell death and is associated with hyperpolarization of mitochondria, contrary to a common mitochondrial depolarization initiated by ROS. Again, the effects are very sensitive to how well the pristine surface of PdNC is preserved, suggesting that PdNC can be used as an apoptosis inducing agent, but only with appropriate drug delivery system. PMID:25886644

  16. Effect of Fe state on electrocatalytic activity of Pd-Fe/C catalyst for oxygen reduction

    International Nuclear Information System (INIS)

    The carbon-supported Pd-Fe catalyst (Pd-Fe/C) is prepared in the H2O/tetrahydrofuran (THF) mixture solvent under the low temperature. The homemade Pd-Fe/C catalyst contains two forms of iron species, alloying and non-alloying Fe. The alloying Fe species is hardly dissolved in 0.5 M H2SO4 solution, while the non-alloying Fe species is easily dissolved in 0.5 M H2SO4 solution. The electrochemical measurements show the electrocatalytic activity of the Pd-Fe/C catalyst with the acid treatment for the oxygen reduction is higher than that of the Pd-Fe/C catalyst without the acid treatment, illustrating that the non-alloying Fe species suppresses the electrocatalytic activity of the Pd-Fe/C catalyst. In contrast, the alloying Fe species promotes the electrocatalytic activity of the Pd-Fe/C catalyst for the oxygen reduction, which is likely attributed to the change of the electron structure of Pd atom and/or bond length of Pd-Pd in the Pd-Fe/C catalyst.

  17. Fine-tuning the activity of oxygen evolution catalysts

    DEFF Research Database (Denmark)

    Paoli, Elisa Antares; Masini, Federico; Frydendal, Rasmus;

    2016-01-01

    Water splitting is hindered by the sluggish kinetics of the oxygen evolution reaction (OER). The choice of materials for this reaction in acid is limited to the platinum group metals; high loading required of these scarce and expensive elements severely limit the scalability of such technology....... Ruthenium oxide is among the best catalysts for OER, however the reported activity and stability can vary tremendously depending on the preparation conditions and pre-treatment. Herein, we investigate the effect of oxidation treatment on mass-selected Ru nanoparticles in the size range between 2 and 10 nm....... The effect of two distinct oxidation pre-treatments on the activity and stability have been investigated: (1) thermal oxidation; and (2) oxidation with an oxygen plasma under vacuum. We report that activity and stability can be tuned by using different oxidation pre-treatments. Thermally oxidized particles...

  18. Changes to coral health and metabolic activity under oxygen deprivation

    Science.gov (United States)

    Richmond, Robert H.

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  19. Activated oxygen alters cerebral microvascular responses in newborn pigs

    Energy Technology Data Exchange (ETDEWEB)

    Leffler, C.W.; Busiia, D.W.; Armstead, W.M.; Mirro, R.; Thelin, O. (Univ. of Tennessee, Memphis (United States))

    1990-02-26

    In piglets, cerebral ischemia/reperfusion blocks prostanoid dependent cerebral vasodilation to hypercapnia (CO{sub 2}) and hypotension but not prostanoid independent dilation to isoproterenol (Isu) or constriction to norepinephrine (NE). Ischemia/reperfusion increases activated-O{sub 2} production by piglet brains. Using cranial windows in piglets, the authors investigated the hypothesis that activated oxygen can block prostanoid dependent cerebral vasodilator responses to CO{sub 2} and hypotension without altering responses to Isu and NE. Exposure to an activated oxygen generating system of xanthine oxidase, hypoxanthine, and Fe that made about 3 times the activated-O{sub 2} on the brain surface as ischemia/reperfusion caused reversible pial arteriolar dilation. After exposure, pial arteriolar dilation was reduced to CO{sub 2} and hypotension but not to Isu. NE constrictor responses were also unaltered. H{sub 2}O{sub 2} or H{sub 2}O{sub 2} + Fe caused constriction followed by reversible dilation. After exposure, pial arteriolar dilation in response to CO{sub 2} and hypotension was not altered. However, addition of xanthine oxidase and hypoxanthine with H{sub 2}O{sub 2} and Fe totally eliminated pial arteriolar dilator responses to CO{sub 2} and hypotension but did not decrease dilation caused by Isu or constriction caused by NE. The authors conclude that activated oxygen could produce the altered prostanoid dependent pial arteriolar responses observed following ischemia in piglets.

  20. Changes to coral health and metabolic activity under oxygen deprivation.

    Science.gov (United States)

    Murphy, James W A; Richmond, Robert H

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  1. The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae.

    Science.gov (United States)

    Kumar, Sanjeev; Christophides, George K; Cantera, Rafael; Charles, Bradley; Han, Yeon Soo; Meister, Stephan; Dimopoulos, George; Kafatos, Fotis C; Barillas-Mury, Carolina

    2003-11-25

    Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads. PMID:14623973

  2. Generation of highly reactive oxygen species by co-adsorption of oxygen and water on metal-supported MgO(100) thinfilms

    CERN Document Server

    Song, Zhenjun

    2015-01-01

    The formation of highly reactive oxygen species (ROS) on metal oxide surfaces have attracted considerable interest due to their diverse applications. In this work, we have performed densi-ty-functional theory calculations to investigate the co-adsorption of oxygen and water on ul-trathin MgO(100) films deposited on Mo(100) substrate. We reveal that the molecular oxygen can be stepwise decomposed completely with the assistance of water. Consequently, a series of highly ROS including superoxide, hydroperoxide, hydroxyl and single oxygen adatom are formed on Mo(100) supported MgO(100) thinfilms. The reaction barriers accompanied by the generation of ROS are reported, and the influence of the thickness of MgO(100) films is also discussed. The most promising routes to produce these fascinating species provide valuable information to understand the importance of synergistic effect, namely the substrate, the co-adorbed species, and the film thickness, in multiphase catalyst design.

  3. Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis

    OpenAIRE

    Murthy, Shubha; Adamcakova-Dodd, Andrea; Perry, Sarah S.; Tephly, Linda A.; Keller, Richard M.; Metwali, Nervana; Meyerholz, David K.; Wang, Yongqiang; Glogauer, Michael; Thorne, Peter S.; Carter, A. Brent

    2009-01-01

    The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1...

  4. Regulation of reactive oxygen species generation under drought conditions in Arabidopsis

    OpenAIRE

    Lee, Sangmin; Park, Chung-Mo

    2012-01-01

    Reactive oxygen species (ROS) are produced when plants are exposed to environmental stresses, such as drought and heat conditions. Oxidative stress imposed by ROS under drought conditions profoundly affects plant growth and development. However, ROS production and scavenging mechanisms under adverse environmental conditions are largely unknown. We have recently reported that a NAM/ATAF1/2/CUC2 (NAC) transcription factor NTL4 is required for generation of ROS under drought conditions in Arabid...

  5. Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species

    OpenAIRE

    Ro, Seung-Hyun; Nam, Myeongjin; Jang, Insook; Park, Hwan-Woo; Park, Haeli; Semple, Ian A.; Kim, Myungjin; Kim, Jeong; Park, Haewon; Einat, Paz; Damari, Golda; Golikov, Maya; Feinstein, Elena; Lee, Jun Hee

    2014-01-01

    Antioxidant therapy was once considered useful for treating metabolic syndrome because excessive accumulation of reactive oxygen species (ROS) was identified as an inducer of diverse metabolic pathologies. However, the effectiveness of dietary antioxidants in treating obesity-associated diseases had been largely controversial in numerous animal and human clinical studies, some of which actually show adverse effects upon antioxidant consumption. Here, we show that Sestrin2 and other antioxidan...

  6. Protection of melatonin against damage of sperm mito-chondrial function induced by reactive oxygen species

    Institute of Scientific and Technical Information of China (English)

    Xue-JunShang; Yu-FengHuang; Zhang-QunYe; XiaoYu; Wan-JiaGu

    2004-01-01

    Aim: To study the mitochondrial function damage of sperm in-duced by reactive oxygen species (ROS) and the protection of melatonin (MLT) against the damage. Methods: Normal function spermatozoa were selected from semen samples by Percoll gradi-ent centrifugation technique. The ROS generated by the hypoxan-thine xanthine oxidase system was incubated with the normal sper-matozoa in the presence or absence of MLT (6 retool/L) for 30 and 60 minutes.

  7. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

    OpenAIRE

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

    Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing ...

  8. Reactive Oxygen Species Generated by NADPH Oxidase 2 and 4 Are Required for Chondrogenic Differentiation*

    OpenAIRE

    Kim, Ki Soon; Choi, Hae Woong; Yoon, Hee Eun; Kim, Ick Young

    2010-01-01

    Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes derived from mouse embryos. The intracellular level of ROS was increased during the differentiation process, which was then blocked by treatment with the RO...

  9. Quantification of environmentally persistent free radicals and reactive oxygen species in atmospheric aerosol particles

    OpenAIRE

    Arangio, Andrea M.; Tong, Haijie; Socorro, Joanna; Pöschl, Ulrich; Shiraiwa, Manabu

    2016-01-01

    Fine particulate matter plays a central role in adverse health effects of air pollution. Inhalation and deposition of aerosol particles in the respiratory tract can lead to the release of reactive oxygen species (ROS), which may cause oxidative stress. In this study, we have detected and quantified a wide range of particle-associated radicals using electron paramagnetic resonance (EPR) spectroscopy. Ambient particle samples were collected using a cascade impactor at a semi-urban site in centr...

  10. Reactive oxygen species (ROS)-induced actin glutathionylation controls actin dynamics in neutrophils

    OpenAIRE

    Sakai, Jiro; Li, Jingyu; Subramanian, Kulandayan K.; Mondal, Subhanjan; Bajrami, Besnik; Hattori, Hidenori; Jia, Yonghui; Dickinson, Bryan C; Zhong, Jia; Ye, Keqiang; Chang, Christopher J.; Ho, Ye-Shih; Zhou, Jun; Luo, Hongbo R.

    2012-01-01

    The regulation of actin dynamics is pivotal for cellular processes such as cell adhesion, migration, and phagocytosis, and thus is crucial for neutrophils to fulfill their roles in innate immunity. Many factors have been implicated in signal-induced actin polymerization, however the essential nature of the potential negative modulators are still poorly understood. Here we report that NADPH oxidase-dependent physiologically generated reactive oxygen species (ROS) negatively regulate actin poly...

  11. Mitochondrial role of Apoptosis-Inducing Factor (AIF): Oxidative Phosphorylation and Reactive Oxygen Species.

    OpenAIRE

    Apostolova, Nadezda

    2008-01-01

    The apoptotic function of Apoptosis-inducing factor (AIF) is well documented in the literature, but its physiological role in the mitochondrion is less certain. Using a small interfering RNA (siRNA) strategy, we studied whether modulation of AIF expression in cultured cells influenced the production of reactive oxygen species (ROS). We found that siAIF-transfected cells had reduced AIF protein levels and this was paralleled by a significant increase in ROS. We tested the genera...

  12. Evolving Concepts of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Disease

    OpenAIRE

    Chen, Kai; Keaney, John F.

    2012-01-01

    Cardiovascular disease continues to be a substantial health-care burden, despite recent treatment advances. Oxidative stress has long been regarded as a key pathophysiological mediator that ultimately leads to CVD including atherosclerosis, hypertension and heart failure. Over the past decade, emerging evidence has shifted our understanding of reactive oxygen species (ROS) from its harmful role to being signaling molecules. Here, we reviewed recent advances in our understanding of ROS that me...

  13. Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria

    OpenAIRE

    Von Bergen, Nicholas H; Koppenhafer, Stacia L.; Douglas R Spitz; Volk, Kenneth A.; Patel, Sonali S.; Roghair, Robert D.; Lamb, Fred S.; Jeffrey L. Segar; Scholz, Thomas D.

    2009-01-01

    Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O2•− (superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered by in utero programming, pregnant ewes were given a 48-h dexamethasone (dexam...

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

    OpenAIRE

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

    2013-01-01

    The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic–eukaryotic cross-talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that comme...

  15. Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage

    OpenAIRE

    Dhillon, Harsharan; Chikara, Shireen; Reindl, Katie M.

    2014-01-01

    Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, pipe...

  16. NADPH Oxidases: A Perspective on Reactive Oxygen Species Production in Tumor Biology

    OpenAIRE

    Meitzler, Jennifer L.; Antony, Smitha; Wu, Yongzhong; Juhasz, Agnes; Liu, Han; Jiang, Guojian; LU, JIAMO; ROY, KRISHNENDU; Doroshow, James H.

    2014-01-01

    Significance: Reactive oxygen species (ROS) promote genomic instability, altered signal transduction, and an environment that can sustain tumor formation and growth. The NOX family of NADPH oxidases, membrane-bound epithelial superoxide and hydrogen peroxide producers, plays a critical role in the maintenance of immune function, cell growth, and apoptosis. The impact of NOX enzymes in carcinogenesis is currently being defined and may directly link chronic inflammation and NOX ROS-mediated tum...

  17. Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

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

    2016-08-19

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

  18. Targeting Mitochondria and Reactive Oxygen Species-Driven Pathogenesis in Diabetic Nephropathy.

    Science.gov (United States)

    Lindblom, Runa; Higgins, Gavin; Coughlan, Melinda; de Haan, Judy B

    2015-01-01

    Diabetic kidney disease is one of the major microvascular complications of both type 1 and type 2 diabetes mellitus. Approximately 30% of patients with diabetes experience renal complications. Current clinical therapies can only mitigate the symptoms and delay the progression to end-stage renal disease, but not prevent or reverse it. Oxidative stress is an important player in the pathogenesis of diabetic nephropathy. The activity of reactive oxygen and nitrogen species (ROS/NS), which are by-products of the diabetic milieu, has been found to correlate with pathological changes observed in the diabetic kidney. However, many clinical studies have failed to establish that antioxidant therapy is renoprotective. The discovery that increased ROS/NS activity is linked to mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, cellular senescence, and cell death calls for a refined approach to antioxidant therapy. It is becoming clear that mitochondria play a key role in the generation of ROS/NS and their consequences on the cellular pathways involved in apoptotic cell death in the diabetic kidney. Oxidative stress has also been associated with necrosis via induction of mitochondrial permeability transition. This review highlights the importance of mitochondria in regulating redox balance, modulating cellular responses to oxidative stress, and influencing cell death pathways in diabetic kidney disease. ROS/NS-mediated cellular dysfunction corresponds with progressive disease in the diabetic kidney, and consequently represents an important clinical target. Based on this consideration, this review also examines current therapeutic interventions to prevent ROS/NS-derived injury in the diabetic kidney. These interventions, mainly aimed at reducing or preventing mitochondrial-generated oxidative stress, improving mitochondrial antioxidant defense, and maintaining mitochondrial integrity, may deliver alternative approaches to halt or prevent diabetic kidney

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

    Energy Technology Data Exchange (ETDEWEB)

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

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

  20. In the idiopathic inflammatory myopathies (IIM), do reactive oxygen species (ROS) contribute to muscle weakness?

    Science.gov (United States)

    Lightfoot, Adam P; McArdle, Anne; Jackson, Malcolm J; Cooper, Robert G

    2015-07-01

    The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders, collectively known as myositis. Affected patients present with proximal muscle weakness, which usually improves following treatment with immunosuppressants, but often incompletely so, thus many patients remain weak. IIMs are characterised histologically by inflammatory cell infiltrates into skeletal muscle and overexpression of major histocompatibility complex I on muscle cell surfaces. Although inflammatory cell infiltrates represent a major feature of myositis there is growing evidence that muscle weakness correlates only poorly with the degree of cellular infiltration, while weakness may in fact precede such infiltrations. The mechanisms underpinning such non-immune cell mediated weakness in IIM are poorly understood. Activation of the endoplasmic reticulum stress pathways appears to be a potential contributor. Data from non-muscle cells indicate that endoplasmic reticulum stress results in altered redox homeostasis capable of causing oxidative damage. In myopathological situations other than IIM, as seen in ageing and sepsis, evidence supports an important role for reactive oxygen species (ROS). Modified ROS generation is associated with mitochondrial dysfunction, depressed force generation and activation of muscle catabolic and autophagy pathways. Despite the growing evidence demonstrating a key role for ROS in skeletal muscle dysfunction in myopathologies other than IIM, no research has yet investigated the role of modified generation of ROS in inducing the weakness characteristic of IIM. This article reviews current knowledge regarding muscle weakness in the absence of immune cells in IIM, and provides a background to the potential role of modified ROS generation as a mechanism of muscle dysfunction. The authors suggest that ROS-mediated mechanisms are potentially involved in non-immune cell mediated weakness seen in IIM and outline how these mechanisms might be

  1. Curcumin-induced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications

    Indian Academy of Sciences (India)

    M Balasubramanyam; A Adaikala Koteswari; R Sampath Kumar; S Finny Monickaraj; J Uma Maheswari; V Mohan

    2003-12-01

    There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.

  2. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai (China); Zhang, Mingming; Song, Shushu [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Institute of Biomedical Science, Fudan University, Shanghai (China)

    2015-08-07

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC.

  3. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    Science.gov (United States)

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  4. Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation

    Directory of Open Access Journals (Sweden)

    Mahesh Subramanian

    2014-01-01

    Full Text Available Resveratrol (5-[(E-2-(4-hydroxyphenylethenyl]benzene-1,3-diol, a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry and propidium iodide uptake (flow cytometry and microscopy as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.

  5. Resveratrol induced inhibition of Escherichia coli proceeds via membrane oxidation and independent of diffusible reactive oxygen species generation.

    Science.gov (United States)

    Subramanian, Mahesh; Goswami, Manish; Chakraborty, Saikat; Jawali, Narendra

    2014-01-01

    Resveratrol (5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol), a redox active phytoalexin with a large number of beneficial activities is also known for antibacterial property. However the mechanism of action of resveratrol against bacteria remains unknown. Due to its extensive redox property it was envisaged if reactive oxygen species (ROS) generation by resveratrol could be a reason behind its antibacterial activity. Employing Escherichia coli as a model organism we have evaluated the role of diffusible reactive oxygen species in the events leading to inhibition of this organism by resveratrol. Evidence for the role of ROS in E. coli treated with resveratrol was investigated by direct quantification of ROS by flow cytometry, supplementation with ROS scavengers, depletion of intracellular glutathione, employing mutants devoid of enzymatic antioxidant defences, induction of adaptive response prior to resveratrol challenge and monitoring oxidative stress response elements oxyR, soxS and soxR upon resveratrol treatment. Resveratrol treatment did not result in scavengable ROS generation in E. coli cells. However, evidence towards membrane damage was obtained by potassium leakage (atomic absorption spectrometry) and propidium iodide uptake (flow cytometry and microscopy) as an early event. Based on the comprehensive evidences this study concludes for the first time the antibacterial property of resveratrol against E. coli does not progress via the diffusible ROS but is mediated by site-specific oxidative damage to the cell membrane as the primary event.

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

    Science.gov (United States)

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

    2013-10-01

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

  7. Determination of reactive oxygen generated from natural medicines and their antibacterial activity$

    Institute of Scientific and Technical Information of China (English)

    Noriko Tajima; Makiko Takasaki; Haruka Fukamachi; Takeshi Igarashi; Yoshijiro Nakajima; Hidetoshi Arakawa

    2016-01-01

    Extracts of 16 natural medicine powders (Galla chinensis, Malloti cortex, Cassiae semen, Sophorae radix, Myricae cortex, Crataegi fructus, Gambir, Mume fructus, Geranii herba, Phellodendri cortex, Coptidis rhizoma, Swertiae herba, and Cinnamomi cortex) were assayed for reactive oxygen concentrations using the per-oxyoxalate chemiluminescent detection system. High luminescence intensity was observed in Galla chinensis, Geranii herba, Malloti cortex, Myricae cortex, and Cinnamomi cortex. Additional experiments identified the reactive oxygen species as hydrogen peroxide. Galla chinensis generated 2.4 ? 10 ? 4 mol/L hydrogen peroxide from a 1 mg/mL solution. In bacterial growth tests, Galla chinensis extract had antibacterial activity against Escherichia coli, Staphylococcus aureus, Bacteroides thetaiotaomicron, Campylobacter sputorum biovar sputorum, Streptococcus salivarius thermophilus, Lactobacillus casei, and Bifidobacterium longum infantis. This antibacterial activity was de-creased by the addition of catalase. It revealed that hydrogen peroxide which Galla chinensis produced participated in antibacterial activity.

  8. Improved oxygen reduction activity on Pt3Ni(111) via increased surface site availability.

    Science.gov (United States)

    Stamenkovic, Vojislav R; Fowler, Ben; Mun, Bongjin Simon; Wang, Guofeng; Ross, Philip N; Lucas, Christopher A; Marković, Nenad M

    2007-01-26

    The slow rate of the oxygen reduction reaction (ORR) in the polymer electrolyte membrane fuel cell (PEMFC) is the main limitation for automotive applications. We demonstrated that the Pt3Ni(111) surface is 10-fold more active for the ORR than the corresponding Pt(111) surface and 90-fold more active than the current state-of-the-art Pt/C catalysts for PEMFC. The Pt3Ni(111) surface has an unusual electronic structure (d-band center position) and arrangement of surface atoms in the near-surface region. Under operating conditions relevant to fuel cells, its near-surface layer exhibits a highly structured compositional oscillation in the outermost and third layers, which are Pt-rich, and in the second atomic layer, which is Ni-rich. The weak interaction between the Pt surface atoms and nonreactive oxygenated species increases the number of active sites for O2 adsorption. PMID:17218494

  9. Antimicrobial activities of selected Cyathus species.

    Science.gov (United States)

    Liu, Ya-Jun; Zhang, Ke-Qin

    2004-02-01

    Twelve selected Cyathus species were tested for their abilities to produce antimicrobial metabolites. Most of them were found to produce secondary exo-metabolites that could induce morphological abnormalities of rice pathogenic fungi Pyricularia oryzae. Some extracts from the cultivated liquid obviously inhibited human pathogenic fungi Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. Activities against six human pathogenic bacteria were also obtained from some of these extracts. PMID:15119855

  10. Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase 2 under mild hypoxia.

    Science.gov (United States)

    Niecknig, Helene; Tug, Suzan; Reyes, Buena Delos; Kirsch, Michael; Fandrey, Joachim; Berchner-Pfannschmidt, Utta

    2012-06-01

    The function and survival of eukaryotic cells depends on a constant and sufficient oxygen supply. Cells recognize and respond to hypoxia by accumulation of the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of an oxygen-sensitive HIF-1α and a constitutive HIF-1β subunit. Besides physiology, HIF-1 induction is involved in major pathological processes such as cardiovascular disease, inflammation and cancer, which are associated with the formation of reactive oxygen species (ROS). ROS have been reported to affect HIF-1 activity but the role for ROS in regulating HIF-1 has not been definitely settled. In order to shed light on the redox-regulation of HIF-1 by ROS, we studied the impact of exogenous ROS treatment (H(2)O(2)) on HIF-1α and HIF-1 regulatory protein prolyl hydroxylase 2 (PHD2) in the human osteosarcoma cell line U2OS. At early reaction periods, H(2)O(2) induced HIF-1α but at prolonged observation phases the opposite occurred. Herein, modulation of PHD activity appeared to be the key element, because knockdown and inhibition of the PHD2 prevented reduction of HIF-1α. However, H(2)O(2) treatment constantly suppressed HIF-1 transactivation at all time-points. Our data indicate a dual redox regulation of HIF-1α protein amount with a constant suppression of HIF-1 target gene expression by ROS. PMID:22360728

  11. Selective Pro-Apoptotic Activity of Novel 3,3′-(Aryl/Alkyl-Methylene)Bis(2-Hydroxynaphthalene-1,4-Dione) Derivatives on Human Cancer Cells via the Induction Reactive Oxygen Species

    Science.gov (United States)

    Sinha, Krishnendu; Brahmachari, Goutam; Sil, Parames C.

    2016-01-01

    Selective induction of apoptosis in cancer cells barring the normal cells is considered as an effective strategy to combat cancer. In the present study, a series of twenty-two (22) synthetic 3,3'-(aryl/alkyl-methylene)bis(2-hydroxynaphthalene-1,4-dione) bis-lawsone derivatives were assayed for their pro-apoptotic activity in six different cell lines (five cancerous and one normal) using MTT assay. Out of these 22 test compounds, 1j was found to be the most effective in inducing apoptosis in human glioma cells (CCF-4) among the different cell lines used in the study. The activity of this compound, 1j, was then compared to a popular anticancer drug, cisplatin, having limited usage because of its nephrotoxic nature. In this study, 1j derivative showed much less toxicity to the normal kidney cells compared to cisplatin, thus indicating the superiority of 1j as a possible anticancer agent. This compound was observed to induce apoptosis in the glioma cells by inducing the caspase dependent apoptotic pathways via ROS and downregulating the PI3K/AKT/mTOR pathway. Estimation of different oxidative stress markers also confirms the induction of oxidative stress in 1j exposed cancer cells. The toxicity of 1j compound toward cancer cells was confirmed further by different flow cytometrical analyses to estimate the mitochondrial membrane potential and cell cycle. The sensitivity of malignant cells to apoptosis, provoked by this synthetic derivative in vitro, deserves further studies in suitable in vivo models. These studies not only identified a novel anticancer drug candidate but also help to understand the metabolism of ROS and its application in cancer treatment. PMID:27380262

  12. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Wang, Fu-Xin [Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002 (China); Ren, Jun [Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071 (United States); Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Zhiming [Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-04-15

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91{sup phox} (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91{sup phox}, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension.

  13. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    International Nuclear Information System (INIS)

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91phox (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91phox, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension

  14. Metabolism of Reactive Oxygen Species in the Cytoplasmic Male-Sterile Cotton Anther

    Institute of Scientific and Technical Information of China (English)

    JIANG Pei-dong; ZHU Yun-guo; WANG Xiao-ling; ZHU Wei; ZHANG Xiao-quan; XIE Hai-yan; WANG Xue-de

    2007-01-01

    Reactive oxygen species (ROS) in plant cell, including superoxide (O2-·), hydrogen peroxide (H2O2), and malondialdehyde (MDA), are thought to be important inducible factors of cell apoptosis if excessively accumulated in cells. To elucidate the metabolic mechanism of ROS production and scavenging in anthers of the cytoplasmic male-sterile (CMS) cotton,CMS line, maintainer, and hybrid F1 anthers, were employed for studying the relationship between CMS and metabolism of ROS, by comparing ROS changes in the sterile and fertile anthers at different developmental stages. The results showed that during the abortion preliminary stage (sporogenous cell division stage), anthers of CMS line had higher contents of O2-·, H2O2, and MDA than those of maintainer or hybrid F1. Simultaneously, the higher activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in scavenging ROS were measured in the anthers of the CMS line,indicating that an increase of ROS in anthers of abortion preliminary stage had an inducible effect on the antioxidant enzymes. But during the abortion peak of CMS anther (pollen mother cell meiosis stage), on the one hand, contents of O2-·,H2O2, and MDA were extraordinarily high in CMS anthers, on the other hand, the activities of SOD, CAT, and POD were excessively low, which disrupted the balance between the production and elimination of ROS and led to pollen mother cells apoptosis at this stage. In the following two stages (uninucleate microspore stage and mature pollen stage), the contents of O2-· and H2O2 in the aborted anthers were approximated to contents in the fertile anthers of the maintainer and hybrid F1. However, MDA contents were continuously raised and enzymic activities of SOD, CAT, and POD were consistently decreased in sterile anthers, which indicated that ROS still had harmful effects on the anthers after the apoptosis of the male cells. Excessive accumulation of O2-·, H2O2, and MDA and significant reduction of ROS

  15. The contraction induced increase in gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator 1alpha (PGC-1alpha), mitochondrial uncoupling protein 3 (UCP3) and hexokinase II (HKII) in primary rat skeletal muscle cells is dependent on reactive oxygen species

    DEFF Research Database (Denmark)

    Silveira, Leonardo R.; Pilegaard, Henriette; Kusuhara, Keiko;

    2006-01-01

    We evaluated the role of reactive oxygen species (ROS) for the contraction induced increase in expression of PGC-1alpha, HKII and UCP3 mRNA. Rat skeletal muscle cells were subjected to acute or repeated electrostimulation in the presence and absence of antioxidants. Contraction of muscle cells lead...

  16. Oxide Defect Engineering Enables to Couple Solar Energy into Oxygen Activation.

    Science.gov (United States)

    Zhang, Ning; Li, Xiyu; Ye, Huacheng; Chen, Shuangming; Ju, Huanxin; Liu, Daobin; Lin, Yue; Ye, Wei; Wang, Chengming; Xu, Qian; Zhu, Junfa; Song, Li; Jiang, Jun; Xiong, Yujie

    2016-07-20

    Modern development of chemical manufacturing requires a substantial reduction in energy consumption and catalyst cost. Sunlight-driven chemical transformation by metal oxides holds great promise for this goal; however, it remains a grand challenge to efficiently couple solar energy into many catalytic reactions. Here we report that defect engineering on oxide catalyst can serve as a versatile approach to bridge light harvesting with surface reactions by ensuring species chemisorption. The chemisorption not only spatially enables the transfer of photoexcited electrons to reaction species, but also alters the form of active species to lower the photon energy requirement for reactions. In a proof of concept, oxygen molecules are activated into superoxide radicals on defect-rich tungsten oxide through visible-near-infrared illumination to trigger organic aerobic couplings of amines to corresponding imines. The excellent efficiency and durability for such a highly important process in chemical transformation can otherwise be virtually impossible to attain by counterpart materials. PMID:27351805

  17. Oxide Defect Engineering Enables to Couple Solar Energy into Oxygen Activation.

    Science.gov (United States)

    Zhang, Ning; Li, Xiyu; Ye, Huacheng; Chen, Shuangming; Ju, Huanxin; Liu, Daobin; Lin, Yue; Ye, Wei; Wang, Chengming; Xu, Qian; Zhu, Junfa; Song, Li; Jiang, Jun; Xiong, Yujie

    2016-07-20

    Modern development of chemical manufacturing requires a substantial reduction in energy consumption and catalyst cost. Sunlight-driven chemical transformation by metal oxides holds great promise for this goal; however, it remains a grand challenge to efficiently couple solar energy into many catalytic reactions. Here we report that defect engineering on oxide catalyst can serve as a versatile approach to bridge light harvesting with surface reactions by ensuring species chemisorption. The chemisorption not only spatially enables the transfer of photoexcited electrons to reaction species, but also alters the form of active species to lower the photon energy requirement for reactions. In a proof of concept, oxygen molecules are activated into superoxide radicals on defect-rich tungsten oxide through visible-near-infrared illumination to trigger organic aerobic couplings of amines to corresponding imines. The excellent efficiency and durability for such a highly important process in chemical transformation can otherwise be virtually impossible to attain by counterpart materials.

  18. Generation and scavenging of reactive oxygen species in wheat flag leaves under combined shading and waterlogging stress

    DEFF Research Database (Denmark)

    Li, Huawei; Cai, Jian; Liu, Fulai;

    2012-01-01

    caused enhanced concentrations of malondialdehyde and H2O2, and an increased superoxide anion release. Superoxide dismutase and catalase activity were stimulated at 4 days after the onset of WS at 0–7 and 8–15 DAA, but decreased at 8 days after the onset of WS at 0–7, 8–15 and 16–23 DAA. Ascorbate...... peroxidase, glutathione reductase, dehydroascorbate reductase and monodehydroascorbate reductase activity increased during 0–8 days after the onset of WS at 0–7, 8–15 and 16–23 DAA. At 16–24 DAA, Pn, the level of reactive oxygen species and activity of the antioxidative enzymes fully recovered in plants...

  19. Epstein-Barr virus infection induces bone resorption in apical periodontitis via increased production of reactive oxygen species.

    Science.gov (United States)

    Jakovljevic, Aleksandar; Andric, Miroslav; Miletic, Maja; Beljic-Ivanovic, Katarina; Knezevic, Aleksandra; Mojsilovic, Slavko; Milasin, Jelena

    2016-09-01

    Chronic inflammatory processes in periapical tissues caused by etiological agents of endodontic origin lead to apical periodontitis. Apart from bacteria, two herpesviruses, Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) are recognized as putative pathogens in apical periodontitis. Although previous reports suggest the involvement of EBV in the pathogenesis of apical periodontitis, its exact role in periapical bone resorption has not yet been fully elucidated. We hypothesize that EBV infection in apical periodontitis is capable of inducing periapical bone resorption via stimulation of reactive oxygen species (ROS) overproduction. Increased levels of ROS induce expression of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). RANKL binding to receptor activator of nuclear factor κB (RANK) present on the surface of preosteoclasts induces their maturation and activation which consequently leads to bone resorption. The potential benefit of antiviral and antioxidant-based therapies in periapical bone resorption treatment remains to be assessed. PMID:27515196

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

    Science.gov (United States)

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

    2015-12-01

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

  1. Reactive oxygen species perpetuate radiation-induced lung injury: causes and cures

    International Nuclear Information System (INIS)

    The risk of unacceptable radiation-induced lung injury remains a significant limiting factor in the current treatment of the tumors involving the thoracic region. Despite advances in normal tissue radiobiology, demonstrating that ionizing radiation triggers a cascade of genetic and molecular events that proceed during a latent period of pulmonary injury, the precise mechanisms underlying radiation-induced lung injury remain unclear. Based on our recent results, we propose a new paradigm of radiation-induced lung injury hypothesizing that hypoxia plays a central role in generating a non-healing wound response that perpetuates radiation lung injury through continuous generation of reactive oxygen species (ROS) and expression/activation of cytokines. Several lines of evidence from our group support this hypothesis. Using electron spin resonance (ESR) and spin trapping we have demonstrated the presence of ROS in rat lungs 13 weeks after irradiation. In a transgenic mouse model we have shown that overexpression of extracellular superoxide dismutase (EC-SOD), an important scavenger of ROS, ameliorates RT-induced lung injury. In addition, our data show that synthetic superoxide dismutase (SOD) mimetic compounds can be used to target ROS and reduce RT-induced lung damage. The findings noted above indicating a role for chronic ROS expression in the perpetuation of a wound healing response, suggest that long term SOD mimetic administration may be an effective therapeutic intervention. This strategy may reduce the risk of radiation-induced lung injury at standard radiation doses and may allow for higher doses of radiation to be delivered to selected tumors without increasing the risk of pulmonary complications

  2. Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin

    Science.gov (United States)

    Herrling, Th.; Jung, K.; Fuchs, J.

    2006-03-01

    Free radicals/reactive oxygen species (ROS) generated in skin by UV irradiation were measured by electron spin resonance (ESR). To increase the sensitivity of measurement the short life free radicals/ROS were scavenged and accumulated by using the nitroxyl probe 3-carboxy-2,2,5,5-tetrametylpyrrolidine-1-oxyl (PCA). The spatial distribution of free radicals/ROS measured in pig skin biopsies with ESR imaging after UV irradiation corresponds to the intensity decay of irradiance in the depth of the skin. The main part of free radicals/ROS were generated by UVA (320-400 nm) so that the spatial distribution of free radicals reaches up to the lower side of the dermis. In vivo measurements on human skin were performed with a L-band ESR spectrometer and a surface coil integrating the signal intensities from all skin layers to get a sufficient signal amplitude. Using this experimental arrangement the protection of UVB and UVA/B filter against the generation of free radicals/ROS in skin were measured. The protection against ROS and the repair of damages caused by them can be realized with active antioxidants characterized by a high antioxidative power (AP). The effect of UV filter and antioxidants corresponding to their protection against free radicals/ROS in skin generated by UVAB irradiation can be quantified by the new radical sun protection factor (RSF). The RSF indicates the increase of time for staying in the sun to generate the same number of free radicals/ROS in the skin like for the unprotected skin. Regarding the amount of generated free radicals/ROS in skin as an biophysical endpoint the RSF characterizes both the protection against UVB and UVA radiation.

  3. Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae.

    Science.gov (United States)

    Ferrándiz, M J; Martín-Galiano, A J; Arnanz, C; Zimmerman, T; de la Campa, A G

    2016-01-01

    We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction. PMID:26525786

  4. Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and Plasmodium.

    Science.gov (United States)

    Molina-Cruz, Alvaro; DeJong, Randall J; Charles, Bradley; Gupta, Lalita; Kumar, Sanjeev; Jaramillo-Gutierrez, Giovanna; Barillas-Mury, Carolina

    2008-02-01

    The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism. PMID:18065421

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

  6. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

    Science.gov (United States)

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-02-26

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  7. Modulation of adipocyte lipogenesis by octanoate: involvement of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Han Jianrong

    2006-07-01

    Full Text Available Abstract Background Octanoate is a medium-chain fatty acid (MCFA that is rich in milk and tropical dietary lipids. It also accounts for 70% of the fatty acids in commercial medium chain triglycerides (MCT. Use of MCT for weight control tracks back to early 1950s and is highlighted by recent clinical trials. The molecular mechanisms of the weight reduction effect remain not completely understood. The findings of significant amounts of MCFA in adipose tissue in MCT-fed animals and humans suggest a direct influence of MCFA on fat cell functions. Methods 3T3-L1 adipocytes were treated with octanoate in a high glucose culture medium supplemented with 10% fetal bovine serum and 170 nM insulin. The effects on lipogenesis, fatty acid oxidation, cellular concentration of reactive oxygen species (ROS, and the expression and activity of peroxisome proliferator receptor gamma (PPARγ and its associated lipogenic genes were assessed. In selected experiments, long-chain fatty acid oleate, PPARγ agonist troglitazone, and antioxidant N-acetylcysteine were used in parallel. Effects of insulin, L-carnitine, and etomoxir on β-oxidation were also measured. Results β-oxidation of octanoate was primarily independent of CPT-I. Treatment with octanoate was linked to an increase in ROS in adipocytes, a decrease in triglyceride synthesis, and reduction of lipogenic gene expression. Co-treatment with troglitazone, N-acetylcysteine, or over-expression of glutathione peroxidase largely reversed the effects of octanoate. Conclusion These findings suggest that octanoate-mediated inactivation of PPARγ might contribute to the down regulation of lipogenic genes in adipocytes, and ROS appears to be involved as a mediator in this process.

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

    Directory of Open Access Journals (Sweden)

    Mohd Farhan

    2016-02-01

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

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

    Science.gov (United States)

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

    2016-02-04

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

  10. Human monocytes tolerant to LPS retain the ability to phagocytose bacteria and generate reactive oxygen species

    Directory of Open Access Journals (Sweden)

    M.L. Fernandes

    2010-09-01

    Full Text Available Tolerance to lipopolysaccharide (LPS occurs when animals or cells exposed to LPS become hyporesponsive to a subsequent challenge with LPS. This mechanism is believed to be involved in the down-regulation of cellular responses observed in septic patients. The aim of this investigation was to evaluate LPS-induced monocyte tolerance of healthy volunteers using whole blood. The detection of intracellular IL-6, bacterial phagocytosis and reactive oxygen species (ROS was determined by flow cytometry, using anti-IL-6-PE, heat-killed Staphylococcus aureus stained with propidium iodide and 2',7'-dichlorofluorescein diacetate, respectively. Monocytes were gated in whole blood by combining FSC and SSC parameters and CD14-positive staining. The exposure to increasing LPS concentrations resulted in lower intracellular concentration of IL-6 in monocytes after challenge. A similar effect was observed with challenge with MALP-2 (a Toll-like receptor (TLR2/6 agonist and killed Pseudomonas aeruginosa and S. aureus, but not with flagellin (a TLR5 agonist. LPS conditioning with 15 ng/mL resulted in a 40% reduction of IL-6 in monocytes. In contrast, phagocytosis of P. aeruginosa and S. aureus and induced ROS generation were preserved or increased in tolerant cells. The phenomenon of tolerance involves a complex regulation in which the production of IL-6 was diminished, whereas the bacterial phagocytosis and production of ROS was preserved. Decreased production of proinflammatory cytokines and preserved or increased production of ROS may be an adaptation to control the deleterious effects of inflammation while preserving antimicrobial activity.

  11. Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

    Science.gov (United States)

    Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

    2016-02-26

    The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

  12. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

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

    Directory of Open Access Journals (Sweden)

    Kang-Kyun Wang

    2013-01-01

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

  14. Studies on the Metabolism of Some Active Oxygen Species in Fruits of Persimmon cv. 'Zaohong' During De-astringency Treatment of Carbon Dioxide%早红柿果实CO2脱涩过程若干活性氧代谢研究

    Institute of Scientific and Technical Information of China (English)

    金光; 廖汝玉; 郭瑞; 周平; 杨凌; 沈清标; 吴绍钟

    2012-01-01

    Fruits of persimmon cv. 'Zaohong; were subjected to de-astringency treatments with carbon dioxide (CO2), and the changes in MDA content, O2- net generation rate, SOD, POD and CAT activities and vitamin C content in them were monitored so as to investigate the effects of CO2 on the metabolism of active oxygen species. MDA content of the fruits rose in the earlier stage of the treatment, reached the maximum and declined thereafter, and the peak occurred earlier with higher CO2 concentration. The net generation rate of O;- showed an increasing trend and decreased only in the 70% and 80; CO2 treatments during the late stage. SOD activity of the fruits increased in the de-astringency treatments with increasing CO2 concentration, the extent of increase being greater in the late stage than in the early stage. POD activity first increased in CO2 treatments and then declined. The changes in POD activity with 70% and 80% CO2 treatments were similar, and the activity was greater with lower CO2 concentration. Higher CAT activity was observed in the CO2 treatment of higher concentration during the early stage, and a decline was detected during the late stage. Vitamin C content kept deceasing except that a slight increase was recorded at the middle stage in the 60; CO2 treatment. The above results suggested that the changes in the indica-tors of active oxygen metabolism were similar to those in tannin content and fruit quality in previous studies, CO2 was the main influencing factor of active oxygen metabolism, and C02 had a positive effect on de-astringency treatment of persimmon fruits.%用CO2对早红柿果实进行脱涩处理,通过对其脱涩过程MDA、O2-净产生速率、SOD、POD、CAT酶活性及抗氧化物质Vc含量变化的研究,探讨CO2对其活性氧代谢的影响,结果表明:CO2处理会使MDA含量增加,均经过一个先上升后下降的过程,且浓度越大,达到峰值的时间越短;O2-净产生速率增大,但脱涩后期80%和70%CO2

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    ), but the extent to which NO might also play a role in the energy metabolism of roots under normal aerobic conditions is unknown. Mitochondria, whose functions are central to aerobic metabolism, are the major source of NO in plants, and potential targets for NO include cytochrome c oxidase in the mitochondrial......Oxygen, the terminal electron acceptor for mitochondrial electron transport, is vital for plants because of its role in the production of ATP by oxidative phosphorylation. While photosynthetic oxygen production contributes to the oxygen supply in leaves, reducing the risk of oxygen limitation...... of mitochondrial metabolism under most conditions, root tissues often suffer oxygen deprivation during normal development due to the lack of an endogenous supply and isolation from atmospheric oxygen. Since changes in oxygen concentration have multiple effects on metabolism and energy production (Geigenberger...

  16. Melatonin enhances mitochondrial ATP synthesis, reduces reactive oxygen species formation, and mediates translocation of the nuclear erythroid 2-related factor 2 resulting in activation of phase-2 antioxidant enzymes (γ-GCS, HO-1, NQO1) in ultraviolet radiation-treated normal human epidermal keratinocytes (NHEK).

    Science.gov (United States)

    Kleszczyński, Konrad; Zillikens, Detlef; Fischer, Tobias W

    2016-09-01

    Melatonin is an ubiquitous molecule with a variety of functions including potent antioxidative properties. Due to its lipophilic character, it easily crosses cellular and intracellular membranes and reaches all subcellular organelles. Because of its ability to scavenge free radicals, melatonin protects against oxidative stress, for example, induced by ultraviolet radiation (UVR). Here, we investigated, in a dose-dependent (0, 10, 25, and 50 mJ/cm(2) ) and time-dependent (0, 4, 24, 48 hr post-UVR) manner, whether melatonin prevents the UVR-mediated alterations in ATP synthesis and the generation of reactive oxygen species (ROS) in normal human epidermal keratinocytes (NHEK). Additionally, we evaluated the molecular mechanism of action of melatonin with regard to activation of phase-2 antioxidative enzymes via nuclear erythroid 2-related factor (Nrf2). We found that (i) melatonin counteracted UVR-induced alterations in the ATP synthesis and reduced free radical formation; (ii) melatonin induced the translocation of Nrf2 transcription factor from the cytosol into the nucleus resulting in, (iii) melatonin enhanced gene expression of phase-2 antioxidative enzymes including γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and NADPH: quinone dehydrogenase-1 (NQO1) representing an elevated antioxidative response of keratinocytes. These results suggest that melatonin not only directly scavenges ROS, but also significantly induces the activation of phase-2 antioxidative enzymes via the Nrf2 pathway uncovering a new action mechanism that supports the ability of keratinocytes to protect themselves from UVR-mediated oxidative stress. PMID:27117941

  17. NADPH oxidase and reactive oxygen species as signaling molecules in carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Gang WANG

    2009-01-01

    Reactive oxygen species (ROS) are small molecule metabolites of oxygen that are prone to participate in redox reactions via their high reactivity. Intracellular ROS could be generated in reduced nicotina-mide-adenine dinucleotidephosphate (NADPH) oxidase-dependent and/or NADPH oxidase-independent manners. Physiologically, ROS are involved in many signaling cascades that contribute to normal processes. One classical example is that ROS derived from the NADPH oxidase and released in neurotrophils are able to digest invading bacteria. Excessive ROS, however, contribute to patho-genesis of various human diseases including cancer, aging, dimentia and hypertension. As signaling messengers, ROS are able to oxidize many targets such as DNA, proteins and lipids, which may be linked with tumor growth, invasion or metastasis. The present review summarizes recent advances in our comprehensive understanding of ROS-linked signaling pathways in regulation of tumor growth, invasion and metastasis, and focuses on the role of the NADPH oxidase-derived ROS in cancer pathogenesis.

  18. Diversity and antibacterial activity of phyllosticta species

    Directory of Open Access Journals (Sweden)

    E. Chukeatirote

    2015-01-01

    Full Text Available Phyllosticta fungi are widely distributed and appear to have different lifestyles. Although some Phyllosticta species are known to cause plant diseases, others are useful due to their bioactive metabolites. In this study, we screened and isolated the Phyllosticta fungi from several plant specimens. In total, 67 Phyllosticta isolates were identified based on their distinct morphological characteristics. Of these, 18 isolates were pathogens and 49 isolates were endophytes. Besides, 61 isolates (91% were identified as P. capitalensis indicating its widespread distribution. Thirty Phyllosticta isolates were then selected for studying their antibacterial activity. For this, the fungal strains were cultured in potato dextrose broth and cultivated at 27 C for 2 weeks. The fungal mycelia were removed and the culture supernatants were extracted using ethyl acetate. Antibacterial activity screening was then carried out using an agar disc diffusion assay. Our data showed that most Phyllosticta crude extracts (87% were active and could inhibit at least one of the testing bacteria.

  19. Application of Activated Carbon Mixed Matrix Membrane for Oxygen Purification

    Directory of Open Access Journals (Sweden)

    Tutuk Djoko Kusworo

    2010-07-01

    Full Text Available This study is performed primarily to investigate the effect of activated carbon on oxygen separation performance of polyethersulfone mixed matrix membrane. In this study, polyethersulfone (PES-activated carbon (AC mixed matrix membranes were fabricated using dry/wet technique. This study investigates the effect of polyethersulfone concentration and activated carbon loading on the performance of mixed matrix membrane in terms of permeability and selectivity of O2/N2 gas separation. The fabricated flat sheet mixed matrix membranes were characterized using permeation test, Field Emission Scanning Electron Microscopy (FESEM analysis and Differential Scanning Calorimetry (DSC. It was found that the activated carbon loading affected the gas separation performance of mixed matrix membrane. PES- 1wt% AC membrane yielded 3.75 of O2/N2 selectivity, however 5 wt% of AC can produced 5 O2/N2 selectivity

  20. AKTIVITAS REACTIVE OXYGEN SPECIES MAKROFAG AKIBAT STIMULASI GEL LIDAH BUAYA PADA INFEKSI Salmonella typhimurium

    Directory of Open Access Journals (Sweden)

    R. Susanti

    2012-09-01

    Full Text Available Reactive Oxygen Species (ROS merupakan salah satu lethal chemical yang dapatmembunuh dan mengeliminasi bakteri pada sel fagosit. Lidah Buaya (Aloevera banyak dipakai sebagai pengobatan tradisional, tetapi belum ada buktiilmiah sampai tingkat seluler apalagi subseluler dalam hal efek imunostimulanpada penyakit infeksi. Tujuan penelitian ini adalah untuk mengetahui aktivitasimunostimulan dari gel lidah buaya yang ditunjukkan oleh aktivitas ROS makrofagsecara in vivo terhadap infeksi bakteri patogen Salmonella typhimurium. Sebanyak24 ekor mencit BABL/c betina umur 8-10 minggu berat 20-30 gram dikelompokkansecara acak menjadi empat kelompok, masing-masing kelompok enam ekor.Kelompok kontrol tidak diberi gel Aloe vera, sementara kelompok P1, P2, dan P3berturut-turut diberi gel Aloe vera 0,5 ml/ekor/hari; 1,0 ml/ekor/hari, dan 1,5ml/ekor/hari. Pemberian gel Aloe vera dilakukan selama sembilan hari. Pada harike-6, mencit diinfeksi bakteri patogen Salmonella typhimurium intraperitoneal105 CFU. Selanjutnya pada hari ke-10 mencit didislokasi dan dibedah, diambilmakrofag dari peritoneum untuk dianalisis produksi ROS-nya. Hasil penelitianmenunjukkan bahwa pemberian gel Aloe vera berpengaruh signi..ikan terhadappeningkatan produksi ROS makrofag mencit BALB/c yang diinfeksi Salmonellatyphimurium. Terdapat perbedaan secara signi..ikan antara kelompok kontroldengan kelompok P1, P2, dan P3, tetapi tidak terdapat perbedaan signi..ikan antarkelompok P1, P2, dan P3. Pemberian gel Aloe vera dosis 0,5 ml/ekor/hari sudahmampu meningkatkan produksi ROS makrofag. Reactive Oxygen Species (ROS is one of lethal chemicals that can kill and eliminatebacteria in phagocytic cells. Aloe vera is widely used as traditional medicine, but thereis no scienti..ic evidence to prove the effect of immunostimulatory of the Aloe vera gel oninfectious disease in the cellular or subcellular level. This research aims to determinethe immunostimulatory activity of Aloe vera gel showed by

  1. Enhanced decomposition of dimethyl phthalate via molecular oxygen activated by Fe-Fe2O3/AC under microwave irradiation

    International Nuclear Information System (INIS)

    Highlights: ► Microwave irradiation induces the electrons transferring from AC to Fe-Fe2O3 and reacts with molecular oxygen. ► Microwave heating accelerates the electron transferring from AC to Fe-Fe2O3 to generate reactive oxygen species. ► This environmental remediation method is feasible for aqueous organic pollutants treatment. - Abstract: In this study, we demonstrate that the decomposition of dimethyl phthalate under microwave irradiation could be greatly enhanced over Fe-Fe2O3 nanowires supported on activated carbon (Fe-Fe2O3/AC). The great enhanced decomposition of dimethyl phthalate could be attributed to a unique microwave induced molecular oxygen activation process. Upon microwave irradiation, electrons could be transferred from activated carbon to zero-valent iron, and then react with molecular oxygen to form O2·− and ·OH radicals for the decomposition of dimethyl phthalate. The deactivation and the regeneration of Fe-Fe2O3/AC catalyst were systematically studied. We also found that microwave heating could accelerate the electron transferring from AC to Fe-Fe2O3 to generate more reactive oxygen species for the decomposition of DMP than conventional oil bath heating. This novel molecular oxygen activation approach may find applications for wastewater treatment and drinking water purification.

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

    Science.gov (United States)

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

  3. Phenol by direct hydroxylation of benzene with nitrous oxide - role of surface oxygen species in the reaction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Reitzmann, A.; Klemm, E.; Emig, G. [Erlangen-Nuernberg Univ., Erlangen (Germany). Lehrstuhl fuer Technische Chemie 1; Buchholz, S.A.; Zanthoff, H.W. [Bochum Univ. (Germany). Inst. of Technical Chemistry

    1998-12-31

    Transient experiments in a Temporal Analysis of Products (TAP) Reactor were performed to elucidate the role of surface oyxgen species in the oxidation of benzene to phenol on ZSM-5 type zeolites with nitrous oxide as a selective oxidant. It was shown by puls experiments with nitrous oxide that the mean lifetime of the generated surface oxygen species is between 0.2s at 500 C and about 4.2 s at 400 C. Afterwards the surface oxygen species desorb as molecular oxygen into the gas phase where total oxidation will take place if hydrocarbons are present. Dual puls experiments consisting of a nitrous oxide puls followed by a benzene puls allowed studying the reactivity of the surface oxygen species formed during the first puls. The observation of the phenol formation was impeded due to the strong sorption of phenol. Multipulse experiments were necessary to reach a pseudo steady state phenol yield. (orig.)

  4. Formation and action of oxygen activated species in cell cultures

    International Nuclear Information System (INIS)

    The differences of hydrogen peroxide sensibility of mammal cell lineages (man, mouse, chinese hamster) in culture are studied. The cellular survival and the frequency of DNA induced breaks by hydrogen peroxide are analysed. The efficiency of elimination of DNA breaks by cells is determined. The possible relation between the cell capacity of repair and its survival to hydrogen peroxide action is also discussed. (M.A.)

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    and it maintains its ability to catalyze the oxidation of guaiacol with hydrogen peroxide as the electron acceptor, although at a slightly lower rate compared to that of the free enzyme in solution. The embedded enzyme is also capable of catalyzing the peroxidase-oxidase reaction. However, the rate is decreased...... for quantification of hydrogen peroxide and other reactive oxygen species in microenvironments, and we propose that the particles may find use as nanosensors for use in, e.g., living cells. (C) 2007 Elsevier Inc. All rights reserved....

  6. Antioxidant effects of antioxidant biofactor on reactive oxygen species in human gingival fibroblasts

    OpenAIRE

    Matsui, Satoshi; Tsujimoto, Yasuhisa; Ozawa, Toshihiko; Matsushima, Kiyoshi

    2011-01-01

    The purpose of this study was to investigate the effects of antioxidant biofactor (AOB) on reactive oxygen species (ROS). Generation of superoxide radical (O2 •−) and hydroxyl radical (•OH) was determined using an electron spin resonance (ESR) spin-trapping method. AOB was added at different concentrations to these free radical generating systems. The generation of both O2 •− and •OH was scavenged by the addition of AOB in a dose-dependent manner. These results indicate that AOB has strong an...

  7. NQO2 is a reactive oxygen species generating off-target for acetaminophen.

    Science.gov (United States)

    Miettinen, Teemu P; Björklund, Mikael

    2014-12-01

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity.

  8. Phytochemistry and biological activities of Phlomis species.

    Science.gov (United States)

    Limem-Ben Amor, Ilef; Boubaker, Jihed; Ben Sgaier, Mohamed; Skandrani, Ines; Bhouri, Wissem; Neffati, Aicha; Kilani, Soumaya; Bouhlel, Ines; Ghedira, Kamel; Chekir-Ghedira, Leila

    2009-09-01

    The genus Phlomis L. belongs to the Lamiaceae family and encompasses 100 species native to Turkey, North Africa, Europe and Asia. It is a popular herbal tea enjoyed for its taste and aroma. Phlomis species are used to treat various conditions such as diabetes, gastric ulcer, hemorrhoids, inflammation, and wounds. This review aims to summarize recent research on the phytochemistry and pharmacological properties of the genus Phlomis, with particular emphasis on its ethnobotanical uses. The essential oil of Phomis is composed of four chemotypes dominated by monoterpenes (alpha-pinene, limonene and linalool), sesquiterpenes (germacrene D and beta-caryophyllene), aliphalic compounds (9,12,15-octadecatrienoic acid methyl ester), fatty acids (hexadecanoic acid) and other components (trans-phytol, 9,12,15-octadecatrien-1-ol). Flavonoids, iridoids and phenylethyl alcohol constitute the main compounds isolated from Phlomis extracts. The pharmacological activities of some Phlomis species have been investigated. They are described according to antidiabetic, antinociceptive, antiulcerogenic, protection of the vascular system, anti-inflammatory, antiallergic, anticancer, antimicrobial and antioxidant properties. PMID:19563875

  9. Biochemical behaviour of norbixin during in vitro DNA damage induced by reactive oxygen species.

    Science.gov (United States)

    Kovary, K; Louvain, T S; Costa e Silva, M C; Albano, F; Pires, B B; Laranja, G A; Lage, C L; Felzenszwalb, I

    2001-04-01

    Naturally occurring antioxidants such as carotenoids are extensively studied for their potential in reducing the risk for cancer and other chronic diseases. In the present study, the radical-scavenger activity of the food additive norbixin, a water-soluble carotenoid extracted from Bixa orellana seeds and commercialized as annatto, was evaluated under conditions of DNA damage induced by reactive oxygen species, particularly by hydroxyl radicals. The cell-free scavenger activity of norbixin was evaluated using plasmid DNA as target molecule and Sn2+ or Fe2+ as oxidant. The addition of H2O2 enhanced DNA breakage induced by metal ions, particularly Fe2+. Under these conditions, norbixin started to protect plasmid DNA against single- and double-strand breakage at a metal:norbixin ratio of 1:1 (Sn2+) and 1:10 (Fe2+). However, at lower ratios to Sn2+, norbixin enhanced Sn2+-induced DNA breakage (P < 0.05). The ability of norbixin to protect genomic DNA against oxidative damage was assessed in murine fibroblasts submitted to H2O2-induced oxidative stress and the results were evaluated by the comet assay. Under low serum conditions (2 % fetal bovine serum (FBS)), a protective effect of norbixin against H2O2-induced DNA breakage was inversely related to its concentration, a protection ranging from 41 % (10 microm) to 21 % (50 microm). At higher concentrations of norbixin, however, oxidative DNA breakage was still enhanced, even in the presence of a high serum concentration (10 % FBS). Under normal conditions, norbixin per se has no detectable genotoxic or cytotoxic effects on murine fibroblasts. The antimutagenic potential of norbixin against oxidative mutagens was also evaluated by the Salmonella typhimurium assay, with a maximum inhibition of 87 % against the mutagenicity induced by H2O2. Although plasmid DNA and Ames data indicated that norbixin can protect DNA against oxidative damage, it seems to be a risky guardian of genomic DNA as it can also increase the extent of

  10. Occurrence, pathways and implications of biological production of reactive oxygen species in natural waters

    Science.gov (United States)

    Zhang, T.; Hansel, C. M.; Voelker, B. M.; Lamborg, C. H.

    2014-12-01

    Reactive oxygen species (ROS), such as superoxide (O2-) and hydrogen peroxide (H2O2) play a critical role in the redox cycling of both toxic (e.g., Hg) and nutrient (e.g., Fe) metals. Despite the discovery of extracellular ROS production in various microbial cultures, including fungi, algae and bacteria, photo-dependent processes are generally considered as the predominant source of ROS in natural waters. Here we show that biological production of ROS is ubiquitous and occurs at a significant rate in freshwater and brackish water environments. Water samples were collected from three freshwater and one brackish water ponds in Cape Cod, Massachusetts, USA, periodically from 2012 to 2014. Production of O2- and H2O2 were measured in dark incubations of natural water using a chemiluminescent and a colorimetric probe, respectively. Rates of biological ROS production were obtained by comparing unfiltered with 0.2-μm filtered samples. The role of biological activity in ROS production was confirmed by the cessation of ROS production upon addition of formaldehyde. In surface water, production rates of O2- ranged from undetectable to 96.0 ± 30.0 nmol L-1 h-1, and production rates of H2O2 varied between 9.9 ± 1.3 nmol L-1 h-1 and 145.6 ± 11.2 nmol L-1 h-1. The maximum production rates of both ROS were observed in mid-summer 2013, which coincides with peak biological activity. ROS production in the water from aphotic zone was greater than in the water from photic zone. Thus, non-light dependent biological processes are likely the major contributors to ROS production in this system. Moreover, O2- production appeared to be enhanced by NADH and inhibited by proteinase-K, suggesting the possible involvement of NADH oxidoreductases in this process. The potential role of different microbial communities in ROS production, and the implications of biological ROS production for mercury speciation will also be discussed.

  11. Oxygen reduction and evolution at single-metal active sites

    DEFF Research Database (Denmark)

    Calle-Vallejo, F.; Martínez, J.I.; García Lastra, Juan Maria;

    2013-01-01

    A worldwide spread of clean technologies such as low-temperature fuel cells and electrolyzers depends strictly on their technical reliability and economic affordability. Currently, both conditions are hardly fulfilled mainly due to the same reason: the oxygen electrode, which has large overpotent...... may be improved by careful selections of the support and the ligand properties close to the active sites and/or the ramifications near them, so that charge is transferred back and forth during adsorption and selective hydrogen bonds are formed....

  12. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

  13. EPR study on the photosensitized generation of reactive oxygen species by actinomycin D

    Institute of Scientific and Technical Information of China (English)

    PAN; Jingxi; (潘景喜); ZHANG; Suping; (张素萍); TU; Tiecheng; (屠铁成); HAN; Zhenhui; (韩镇辉); CAI; Xichen; (蔡喜臣); YAO; Side; (姚思德); LIN; Nianyun; (林念芸)

    2002-01-01

    Actinomycin D (AMD) is an Received anticancer antibiotic that can bind selectively to both double-stranded and single-stranded DNA, and this binding greatly enhances DNA photosensitization. Using electron paramagnetic resonance (EPR) in combination with spin trapping techniques, a systematic study was carried out on the reactive oxygen species generated in the photosensitization process of AMD. It was found that 1O2 and are important reactive intermediates either in solution or in DNA complexes, and the generation of these species is in competition. This finding suggests that the photodynamic action of AMD proceeds via two pathways: energy transfer (type I mechanism) and electron transfer (type II mechanism). 1O2 is the main product formed via energy transfer reaction in solution while electron transfer between the excited states of AMD and DNA becomes the predominant pathway in DNA complexes.

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

    Science.gov (United States)

    Stork, Christian J; Li, Yang V

    2016-01-01

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

  15. Signaling by carcinogenic metals and metal-induced reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Gabriel Keith; Shi Xianglin

    2003-12-10

    Epidemiological data indicate that exposure to metal and metalloid species, including arsenic (III), chromium (VI), and nickel (II), increases the risk of cancer, particularly of the lung and skin. Alterations in normal signal transduction as a result of exposure to carcinogenic metals, and to metal-catalyzed reactive oxygen species (ROS) formation, appear to play an important role in the etiology of metal-induced carcinogenesis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases, and nuclear transcription factors. This article reviews current literature on the effects of carcinogenic metals and metal-induced ROS on cancer-related signaling pathways. In addition, the mechanisms by which those changes occur, and the role of those changes in carcinogenesis are discussed.

  16. H2O2-induced Leaf Cell Death and the Crosstalk of Reactive Nitric/Oxygen Species([F])

    Institute of Scientific and Technical Information of China (English)

    Yiqin Wang; Aihong Lin; Gary J.Loake; Chengcai Chu

    2013-01-01

    In plants,the chloroplast is the main reactive oxygen species (ROS) producing site under high light stress.Catalase (CAT),which decomposes hydrogen peroxide (H2O2),is one of the controlling enzymes that maintains leaf redox homeostasis.The catalase mutants with reduced leaf catalase activity from different plant species exhibit an H2O2-induced leaf cell death phenotype.This phenotype was differently affected by light intensity or photoperiod,which may be caused by plant species,leaf redox status or growth conditions.In the rice CAT mutant nitric oxide excess 1 (noe1),higher H2O2 levels induced the generation of nitric oxide (NO) and higher S-nitrosothiol (SNO) levels,suggesting that NO acts as an important endogenous mediator in H2O2-induced leaf cell death.As a free radical,NO could also react with other intracellular and extracellular targets and form a series of related molecules,collectively called reactive nitrogen species (RNS).Recent studies have revealed that both RNS and ROS are important partners in plant leaf cell death.Here,we summarize the recent progress on H2O2-induced leaf cell death and the crosstalk of RNS and ROS signals in the plant hypersensitive response (HR),leaf senescence,and other forms of leaf cell death triggered by diverse environmental conditions.

  17. The Effect of Polyunsaturated Aldehydes on Skeletonema marinoi (Bacillariophyceae: The Involvement of Reactive Oxygen Species and Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Alessandra A. Gallina

    2014-07-01

    Full Text Available Nitric oxide (NO and reactive oxygen species (ROS production was investigated in the marine diatom, Skeletonema marinoi (SM, exposed to 2E,4E/Z-decadienal (DECA, 2E,4E/Z-octadienal (OCTA, 2E,4E/Z-heptadienal (HEPTA and a mix of these last two (MIX. When exposed to polyunsaturated aldehydes (PUA, a decrease of NO was observed, proportional to the PUA concentration (85% of the initial level after 180 min with 66 µM DECA. Only OCTA, HEPTA and MIX induced a parallel increase of ROS, the highest (2.9-times the control with OCTA concentrations twice the EC50 for growth at 24 h (20 μM. The synthesis of carotenoids belonging to the xanthophyll cycle (XC was enhanced during exposure, suggesting their antioxidant activity. Our data provide evidence that specific pathways exist as a reaction to PUA and that they depend upon the PUA used and/or the diatom species. In fact, Phaeodactylum tricornutum (PT produces NO in response to DECA, but not to OCTA. We advance the hypothesis that SM perceives OCTA and HEPTA as intra-population infochemicals (as it produces PUA, while PT (non-PUA producing species perceives them as allelochemicals. The ability to produce and to use PUA as infochemicals may underlie ecological traits of different diatom species and modulate ecological success in natural communities.

  18. Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Wang H

    2014-06-01

    Full Text Available Haiping Wang,1 Xiaobing Wang,1 Shaoliang Zhang,2 Pan Wang,1 Kun Zhang,1 Quanhong Liu1 1Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, 2Qinglong High-Tech Co, Ltd, Yichun, Jiangxi, People's Republic of China Background: Sonodynamic therapy (SDT is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS, and its sonotoxicity in an esophageal cancer (ECA-109 cell line. Methods: The fluorescence intensity of DVDMS, hematoporphyrin, protoporphyrin IX, and Photofrin II was detected by fluorescence microscopy and flow cytometry. Generation of singlet oxygen was measured using a 1, 3-diphenylisobenzofuran experiment. A 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide assay was used to examine cell viability. Production of reactive oxygen species (ROS and destabilization of the mitochondrial membrane potential were assessed by flow cytometry. Apoptosis was analyzed using Annexin-PE/7-amino-actinomycin D staining. Confocal microscopy was performed to assess mitochondrial damage and identify release of cytochrome C after treatment. Western blots were used to determine expression of oxidative stress-related and apoptosis-associated protein. Ultrastructural changes in the cell were studied by scanning electron microscopy. Results: DVDMS showed higher autofluorescence intensity and singlet oxygen production efficiency compared with other photosensitizers in both cancerous and normal cells. Compared with hematoporphyrin, DVDMS-mediated SDT was more cytotoxic in ECA-109 cells. Abundant intracellular ROS was found in the SDT groups, and the cytotoxicity

  19. Caspase-3-dependent apoptosis of citreamicin ε-induced heLa iells Is associated with reactive oxygen species generation

    KAUST Repository

    Liu, Lingli

    2013-07-15

    Citreamicins, members of the polycyclic xanthone family, are promising antitumor agents that are produced by Streptomyces species. Two diastereomers, citreamicin ε A (1) and B (2), were isolated from a marine-derived Streptomyces species. The relative configurations of these two diastereomers were determined using NMR spectroscopy and successful crystallization of citreamicin ε A (1). Both diastereomers showed potent cytotoxic activity against HeLa (cervical cancer) and HepG2 (hepatic carcinoma) cells with IC 50 values ranging from 30 to 100 nM. The terminal deoxynucleotidyl transferase dUTP nick-end labeling assay confirmed that citreamicin ε A (1) induced cellular apoptosis, and Western blot analysis showed that apoptosis occurred via activation of caspase-3. The 2,7-dichlorofluorescein diacetate assay indicated that citreamicin ε substantially increased the intracellular concentration of reactive oxygen species (ROS). To confirm the hypothesis that citreamicin ε induced apoptosis through an increase in the intracellular ROS concentration, the oxidized products, oxicitreamicin ε A (3) and B (4), were obtained from a one-step reaction catalyzed by Ag 2O. These products, with a reduced capacity to increase the intracellular ROS concentration, exhibited a significantly weakened cytotoxicity in both HeLa and HepG2 cells compared with that of citreamicin ε A (1) and B (2). © 2013 American Chemical Society.

  20. Hemoglobin induces colon cancer cell proliferation by release of reactive oxygen species

    Institute of Scientific and Technical Information of China (English)

    Ryung-Ah Lee; Hyun-Ah Kim; Bo-Young Kang; Kwang-Ho Kim

    2006-01-01

    AIM: To study whether hemoglobin could amplify colon cancer cell proliferation via reactive oxygen species (ROS)production.METHODS: Colon cancer cell line HT-29 was grown in the conventional method using RPMI1640 media. The viability of the cells was measured using the colorimetric MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay after adding hemoglobin. We determined reactive oxygen species levels to be indicators of oxidative stress in HT 29 cell lines with and without hemoglobin and/or 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5-DFUR) using fluorometric dichlorofluorescin diacetate (DCFH-DA) assay.RESULTS: Cellular proliferation was increased with hemoglobin in a concentration-dependent manner. A significant increment on ROS levels was found in HT 29 cells following hemoglobin incubation. The cytotoxic effects of 5-FU and 5-DFUR were significantly blunted by administration of hemoglobin. There was a slight increase of peroxiredoxin 1, superoxide dismutase 1 concentration according to different hemoglobin concentrations.CONCLUSION: Hemoglobin has a cellular proliferative effect on HT-29 colon cancer cell line by production of ROS. Also, hemoglobin abates cytotoxic effects of chemotherapeutic agents such as 5-FU and 5-DFUR.

  1. Formation of reactive oxygen species in rat epithelial cells upon stimulation with fly ash

    Indian Academy of Sciences (India)

    K Voelkel; H F Krug; S Diabaté

    2003-02-01

    Fly ash was used as a model for ambient particulate matter which is under suspicion to cause adverse pulmonary health effects. The fly ash was pre-sized and contained only particles < 20 m including an ultrafine fraction (< 100 nm) that contributed 31% to the particle number. In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the formation of ROS with regard to the mass of particles applied. Lipopolysaccharide (LPS) added as a co-stimulus did not increase the formation of ROS induced by fly ash. Furthermore, in LPS (0.1 g/ml) and tumour necrosis factor-alpha (TNF-alpha; 1 ng/ml) pre-treated cells no increase in reactive oxygen species comparable to fly ash alone is observable. In presence of the metal chelator, desferrioxamine (DFO), ROS formation can be significantly reduced. Neither fly ash nor LPS induced a significant NO release in RLE-6TN cells.

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

    Directory of Open Access Journals (Sweden)

    Felipe A Arenas

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

  3. Production characteristics of reactive oxygen/nitrogen species in water using atmospheric pressure discharge plasmas

    Science.gov (United States)

    Takahashi, Kazuhiro; Satoh, Kohki; Itoh, Hidenori; Kawaguchi, Hideki; Timoshkin, Igor; Given, Martin; MacGregor, Scott

    2016-07-01

    A pulsed discharge, a DC corona discharge, and a plasma jet are separately generated above a water surface, and reactive oxygen species and reactive nitrogen species (ROS/RNS) in the water are investigated. ROS/RNS in water after the sparging of the off-gas of a packed-bed dielectric barrier discharge (PB-DBD) are also investigated. H2O2, NO2 ‑, and NO3 ‑ are detected after plasma exposure and only NO3 ‑ after off-gas sparging. Short-lifetime species in plasma are found to play an important role in H2O2 and NO2 ‑ production and long-lifetime species in NO3 ‑ production. NO x may inhibit H2O2 production through OH consumption to produce HNO2 and HNO3. O3 does not contribute to ROS/RNS production. The pulsed plasma exposure is found to be effective for the production of H2O2 and NO2 ‑, and the off-gas sparging of the PB-DBD for the production of NO3 ‑.

  4. Science Letters:Effect of nitrogen doping on the reduction of nitric oxide with activated carbon in the presence of oxygen

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Nitrogen doping of activated carbon (AC) was performed by annealing both in ammonia and nitric oxide, and the activities of the modified carbons for NO reduction were studied in the presence of oxygen. Results show that nitrogen atoms were incorporated into the carbons, mostly in the form of pyridinic nitrogen or pyridonic nitrogen. The effect of nitrogen doping on the activities of the carbons can be ignored when oxygen is absent, but the doped carbons show desirable activities in the low temperature regime (≤500 ℃) when oxygen is present. The role of the surface nitrogen species is suggested to promote the formation of NO2 in the presence of oxygen, and NO2 can facilitate decomposition of the surface oxygen species in the low temperature regime.

  5. Organic aerosols associated with the generation of reactive oxygen species (ROS) by water-soluble PM2.5.

    Science.gov (United States)

    Verma, Vishal; Fang, Ting; Xu, Lu; Peltier, Richard E; Russell, Armistead G; Ng, Nga Lee; Weber, Rodney J

    2015-04-01

    We compare the relative toxicity of various organic aerosol (OA) components identified by an aerosol mass spectrometer (AMS) based on their ability to generate reactive oxygen species (ROS). Ambient fine aerosols were collected from urban (three in Atlanta, GA and one in Birmingham, AL) and rural (Yorkville, GA and Centerville, AL) sites in the Southeastern United States. The ROS generating capability of the water-soluble fraction of the particles was measured by the dithiothreitol (DTT) assay. Water-soluble PM extracts were further separated into the hydrophobic and hydrophilic fractions using a C-18 column, and both fractions were analyzed for DTT activity and water-soluble metals. Organic aerosol composition was measured at selected sites using a high-resolution time-of-flight AMS. Positive matrix factorization of the AMS spectra resolved the organic aerosol into isoprene-derived OA (Isop_OA), hydrocarbon-like OA (HOA), less-oxidized oxygenated OA, (LO-OOA), more-oxidized OOA (MO-OOA), cooking OA (COA), and biomass burning OA (BBOA). The association of the DTT activity of water-soluble PM2.5 (WS_DTT) with these factors was investigated by linear regression techniques. BBOA and MO-OOA were most consistently linked with WS_DTT, with intrinsic water-soluble activities of 151 ± 20 and 36 ± 22 pmol/min/μg, respectively. Although less toxic, MO-OOA was most widespread, contributing to WS_DTT activity at all sites and during all seasons. WS_DTT activity was least associated with biogenic secondary organic aerosol. The OA components contributing to WS_DTT were humic-like substances (HULIS), which are abundantly emitted in biomass burning (BBOA) and include highly oxidized OA from multiple sources (MO-OOA). Overall, OA contributed approximately 60% to the WS_DTT activity, with the remaining probably from water-soluble metals, which were mostly associated with the hydrophilic WS_DTT fraction. PMID:25748105

  6. A mutation in the mitochondrial protein UQCRB promotes angiogenesis through the generation of mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Junghwa [Chemical Genomics National Research Lab., Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Jung, Hye Jin [Department of Pharmaceutical Engineering, Sun Moon University, Asansi, Chungnam 330-150 (Korea, Republic of); Jeong, Seung Hun; Kim, Hyoung Kyu; Han, Jin [National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Department of Health Sciences and Technology, Cardiovascular and Metabolic Disease Center, Inje University, Busan (Korea, Republic of); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Lab., Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2014-12-12

    Highlights: • We constructed mitochondrial protein UQCRB mutant stable cell lines on the basis of a human case report. • These mutant cell lines exhibit pro-angiogenic activity with enhanced VEGF expression. • Proliferation of mutant cell lines was regulated by UQCRB inhibitors. • UQCRB may have a functional role in angiogenesis. - Abstract: Ubiquinol-cytochrome c reductase binding protein (UQCRB) is one of the subunits of mitochondrial complex III and is a target protein of the natural anti-angiogenic small molecule terpestacin. Previously, the biological role of UQCRB was thought to be limited to the maintenance of complex III. However, the identification and validation of UQCRB as a target protein of terpestacin enabled the role of UQCRB in oxygen sensing and angiogenesis to be elucidated. To explore the biological role of this protein further, UQCRB mutant stable cell lines were generated on the basis of a human case report. We demonstrated that these cell lines exhibited glycolytic and pro-angiogenic activities via mitochondrial reactive oxygen species (mROS)-mediated HIF1 signal transduction. Furthermore, a morphological abnormality in mitochondria was detected in UQCRB mutant stable cell lines. In addition, the proliferative effect of the UQCRB mutants was significantly regulated by the UQCRB inhibitors terpestacin and A1938. Collectively, these results provide a molecular basis for UQCRB-related biological processes and reveal potential key roles of UQCRB in angiogenesis and mitochondria-mediated metabolic disorders.

  7. Mitochondrial reactive oxygen species production by fish muscle mitochondria: Potential role in acute heat-induced oxidative stress.

    Science.gov (United States)

    Banh, Sheena; Wiens, Lilian; Sotiri, Emianka; Treberg, Jason R

    2016-01-01

    Acute heat challenge is known to induce cell-level oxidative stress in fishes. Mitochondria are well known for the capacity to make reactive oxygen species (ROS) and as such are often implicated as a source of the oxidants associated with this thermally-induced oxidative stress. This implication is often asserted, despite little direct data for mitochondrial ROS metabolism in fishes. Here we characterize mitochondrial ROS metabolism in three Actinopterygian fish species at two levels, the capacity for superoxide/H2O2 production and the antioxidant thiol-reductase enzyme activities. We find that red muscle mitochondria from all three species have measurable ROS production and respond to different assay conditions consistent with what might be anticipated; assuming similar relative contributions from difference ROS producing sites as found in rat skeletal muscle mitochondria. Although there are species and assay specific exceptions, fish mitochondria may have a greater capacity to produce ROS than that found in the rat when either normalized to respiratory capacity or determined at a common assay temperature. The interspecific differences in ROS production are not correlated with thiol-based antioxidant reductase activities. Moreover, mimicking an acute in vivo heat stress by comparing the impact of increasing assay temperature on these processes in vitro, we find evidence supporting a preferential activation of mitochondrial H2O2 production relative to the increase in the capacity of reductase enzymes to supply electrons to the mitochondrial matrix peroxidases. This supports the contention that mitochondria may be, at least in part, responsible for the ROS that lead to oxidative stress in fish tissues exposed to acute heat challenge.

  8. NADPH oxidase-dependent production of reactive oxygen species induces endoplasmatic reticulum stress in neutrophil-like HL60 cells.

    Directory of Open Access Journals (Sweden)

    Wilson Mitsuo Tatagiba Kuwabara

    Full Text Available Reactive oxygen species (ROS primarily produced via NADPH oxidase play an important role for killing microorganisms in neutrophils. In this study we examined if ROS production in Human promyelocytic leukemia cells (HL60 differentiated into neutrophil-like cells (dHL60 induces ER stress and activates the unfolded protein response (UPR. To cause ROS production cells were treated with PMA or by chronic hyperglycemia. Chronic hyperglycemia failed to induce ROS production and did not cause activation of the UPR in dHL60 cells. PMA, a pharmacologic NADPH oxidase activator, induced ER stress in dHL60 cells as monitored by IRE-1 and PERK pathway activation, and this was independent of calcium signaling. The NADPH oxidase inhibitor, DPI, abolished both ROS production and UPR activation. These results show that ROS produced by NADPH oxidase induces ER stress and suggests a close association between the redox state of the cell and the activation of the UPR in neutrophil-like HL60 cells.

  9. Reactive oxygen species and lipoxygenases regulate the oncogenicity of NPM-ALK-positive anaplastic large cell lymphomas.

    Science.gov (United States)

    Thornber, K; Colomba, A; Ceccato, L; Delsol, G; Payrastre, B; Gaits-Iacovoni, F

    2009-07-23

    The chimera nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the tyrosine kinase activity of which is constitutively upregulated, is the causative agent of 75% of the anaplastic large-cell lymphomas (ALCLs). We have demonstrated that NPM-ALK induces the production of reactive oxygen species (ROS) by a pathway involving the arachidonic acid-metabolizing enzymes of the lipoxygenase (LOX) family. The use of the LOX inhibitor nordihydroguaiaretic acid (NDGA) and of the anti-oxidant N-acetylcysteine (NAC) demonstrated that ROS are important in maintaining the ALK kinase active. Consistent with this, NDGA treatment resulted in the inhibition of key pathways, such as Akt, signal transducer and activator of transcription factor 3 (STAT3) and extracellular signal-regulated kinase (ERK), which are involved in NPM-ALK antiapoptotic and pro-mitogenic functions. Conversely, the stress-activated kinase p38, described in some instances as a mediator of apoptosis, was activated. Interestingly, 5-LOX, an isoform involved in many cancers, was found to be activated in NPM-ALK(+) cells. Functional studies have shown that transforming properties, namely proliferation and resistance to apoptosis, were abrogated by treatment with either NDGA or the 5-LOX inhibitor (N-(3-phenoxycinnamyl)-acetohydroxamic acid) (BW A4C). Together, these data point to the ROS/LOX pathway as a potential new target for therapy in NPM-ALK-positive tumors.

  10. Reactive oxygen species are related to ionic fluxes and volume decrease in apoptotic cerebellar granule neurons: role of NOX enzymes.

    Science.gov (United States)

    Hernández-Enríquez, Berenice; Guemez-Gamboa, Alicia; Morán, Julio

    2011-05-01

    Reactive oxygen species (ROS) are produced early during apoptosis of cerebellar granule neurons induced by low potassium (K5) and staurosporine (Sts). In addition, K5 and Sts activate NADPH oxidases (NOX). Recently, we described that K5 and Sts induce apoptotic volume decrease (AVD) at a time when ROS generation and NOX activity occur. In the present study, we evaluated the relationship between ROS generation and ionic fluxes during AVD. Here, we showed that K5- and Sts-induced AVD was inhibited by antioxidants and that direct ROS production induced AVD. Moreover, NOX inhibitors eliminated AVD induced by both K5 and Sts. Sts, but not K5, failed to induce AVD in cerebellar granule neurons from NOX2 knockout mice. These findings suggest that K5- and Sts-induced AVD is largely mediated by ROS produced by NOX. On the other hand, we also found that the blockage of ionic fluxes involved in AVD inhibited both ROS generation and NOX activity. These findings suggest that ROS generation and NOX activity are involved in ionic fluxes activation, which in turn could maintain ROS generation by activating NOX, leading to a self-amplifying cycle.

  11. NRROS Negatively Regulates Osteoclast Differentiation by Inhibiting RANKL-Mediated NF-N:B and Reactive Oxygen Species Pathways.

    Science.gov (United States)

    Kim, Jung Ha; Kim, Kabsun; Kim, Inyoung; Seong, Semun; Kim, Nacksung

    2015-10-01

    Negative regulator of reactive oxygen species (NRROS) is known to repress ROS generation in phagocytes. In this study, we examined the roles of NRROS in both osteoclasts and osteoblasts. Our results demonstrate that NRROS negatively regulates the differentiation of osteoclasts, but not osteoblasts. Further, overexpression of NRROS in osteoclast precursor cells attenuates RANKL-induced osteoclast differentiation. Conversely, osteoclast differentiation is enhanced upon siRNA-mediated knockdown of NRROS. Additionally, NRROS attenuates RANKL-induced NF-N:B activation, as well as degradation of the NOX1 and NOX2 proteins, which are required for ROS generation. Based on our observations, we present NRROS as a novel negative regulator of RANKL-induced osteoclastogenesis.

  12. Reactive oxygen species involved in apoptosis induction of human respiratory epithelial (A549) cells by Streptococcus agalactiae.

    Science.gov (United States)

    da Costa, Andréia Ferreira Eduardo; Moraes, João Alfredo; de Oliveira, Jessica Silva Santos; dos Santos, Michelle Hanthequeste Bittencourt; Santos, Gabriela da Silva; Barja-Fidalgo, Christina; Mattos-Guaraldi, Ana Luiza; Nagao, Prescilla Emy

    2016-01-01

    Streptococcus agalactiae (Group B Streptococcus; GBS) is an important pathogen and is associated with pneumonia, sepsis and meningitis in neonates and adults. GBS infections induce cytotoxicity of respiratory epithelial cells (A549) with generation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential (ψm). The apoptosis of A549 cells by GBS was dependent on the activation of caspase-3 and caspase-9 with increased pro-apoptotic Bim and Bax molecules and decreased Bcl-2 pro-survival protein. Treatment of infected A549 cells with ROS inhibitors (diphenyleniodonium chloride or apocynin) prevented intracellular ROS production and apoptosis. Consequently, oxidative stress is included among the cellular events leading to apoptosis during GBS human invasive infections. PMID:26490153

  13. Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract

    Science.gov (United States)

    Lakey, Pascale S. J.; Berkemeier, Thomas; Tong, Haijie; Arangio, Andrea M.; Lucas, Kurt; Pöschl, Ulrich; Shiraiwa, Manabu

    2016-09-01

    Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases. Ambient ozone readily saturates the ELF and can enhance oxidative stress by depleting antioxidants and surfactants. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air.

  14. Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract.

    Science.gov (United States)

    Lakey, Pascale S J; Berkemeier, Thomas; Tong, Haijie; Arangio, Andrea M; Lucas, Kurt; Pöschl, Ulrich; Shiraiwa, Manabu

    2016-01-01

    Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases. Ambient ozone readily saturates the ELF and can enhance oxidative stress by depleting antioxidants and surfactants. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air. PMID:27605301

  15. Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract

    Science.gov (United States)

    Lakey, Pascale S. J.; Berkemeier, Thomas; Tong, Haijie; Arangio, Andrea M.; Lucas, Kurt; Pöschl, Ulrich; Shiraiwa, Manabu

    2016-01-01

    Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases. Ambient ozone readily saturates the ELF and can enhance oxidative stress by depleting antioxidants and surfactants. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air. PMID:27605301

  16. A Near-Infrared Triggered Nanophotosensitizer Inducing Domino Effect on Mitochondrial Reactive Oxygen Species Burst for Cancer Therapy.

    Science.gov (United States)

    Yu, Zhengze; Sun, Qiaoqiao; Pan, Wei; Li, Na; Tang, Bo

    2015-11-24

    Photodynamic therapy (PDT) is a well-established modality for cancer therapy, which locally kills cancer cells when light irradiates a photosensitizer. However, conventional PDT is often limited by the extremely short lifespan and severely limited diffusion distance of reactive oxygen species (ROS) generated by photosensitizer, as well as the penetration depth of visible light activation. Here, we develop a near-infrared (NIR) triggered nanophotosensitizer based on mitochondria targeted titanium dioxide-coated upconversion nanoparticles for PDT against cancer. When irradiated by NIR laser, the nanophotosensitizer could produce ROS in mitochondria, which induced the domino effect on ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. Confocal fluorescence imaging indicated that the mitochondrial targeting and real-time imaging of ROS burst could be achieved in living cells. The complete removal of tumor in vivo confirmed the excellent therapeutic effect of the nanophotosensitizer.

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

    Science.gov (United States)

    Flores, Rosa M; Doskey, Paul V

    2015-10-30

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

  18. Effect of Cd,Pb Stress on the Activated Oxygen Scavenging System in Tobacco Levves

    Institute of Scientific and Technical Information of China (English)

    严重玲; 洪业汤; 等

    1998-01-01

    The effect of Cd,Pb stress on the activated oxygen scavenging system indicates that the content of chlorophyll.chlorophyll a/b ratio and the activity of CAT gradually decrease,the activity of SOD increases first and then decreases,and the activity of POd Gradually in creases with incrasing concentrations of Cd and Pb,Between Cd and Pb there is synergism in the Activated oxygen scavenging system.The results show that the stress of Cd and Pb can affect the scavenging system of activated oxygen and result in imbalance of activated oxygen metabolism.

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

    Science.gov (United States)

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

    2015-08-01

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

  20. Ultrastable BSA-capped gold nanoclusters with a polymer-like shielding layer against reactive oxygen species in living cells

    Science.gov (United States)

    Zhou, Wenjuan; Cao, Yuqing; Sui, Dandan; Guan, Weijiang; Lu, Chao; Xie, Jianping

    2016-05-01

    The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells.The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells. Electronic supplementary information (ESI) available: Detailed experimental materials, apparatus, experimental procedures and characterization data. See DOI: 10.1039/c6nr02178f

  1. The antileishmanial activity of novel oxygenated chalcones and their mechanism of action

    DEFF Research Database (Denmark)

    Zhai, L; Chen, M; Blom, J;

    1999-01-01

    Our previous studies have shown that licochalcone A, an oxygenated chalcone, has antileishmanial and antimalarial activities, and alters the ultrastructure and function of the mitochondria of Leishmania spp. parasites. The present study was designed to investigate the antileishmanial activity...... and the mechanism of action of a group of new oxygenated chalcones. The tested oxygenated chalcones inhibited the in-vitro growth of Leishmania major promastigotes and Leishmania donovani amastigotes. Treatment of hamsters infected with L. donovani with intraperitoneal administration of two oxygenated chalcones...

  2. Oxygen reduction reaction activity on Pt{111} surface alloys.

    Science.gov (United States)

    Attard, Gary A; Brew, Ashley; Ye, Jin-Yu; Morgan, David; Sun, Shi-Gang

    2014-07-21

    PtM overlayers (where M=Fe, Co or Ni) supported on Pt{111} are prepared via thermal annealing in either a nitrogen/water or hydrogen ambient of dilute aqueous droplets containing M(Z+) cations directly attached to the electrode. Two different PtM phases are detected depending on the nature of the post-annealing cooling environment. The first of these consists of small (hydroxides. The second type of PtM phase is prepared by cooling in a stream of hydrogen gas. Although this second phase also consists of numerous microcrystals covering the Pt{111} electrode surface, these are both flatter than before and moreover are entirely metallic in character. A positive shift in the onset of PtM oxide formation correlates with increased activity towards the oxygen reduction reaction (ORR), which we ascribe to the greater availability of platinum metallic sites under ORR conditions. PMID:24986646

  3. Apoptosis induction of U937 human leukemia cells by diallyl trisulfide induces through generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Choi Yung

    2012-05-01

    Full Text Available Abstract Background Diallyl trisulfide (DATS is one of the major constituents in garlic oil and has demonstrated various pharmacological activities, including antimicrobial, antihyperlipidemic, antithrombotic, and anticancer effects. However, the mechanisms of antiproliferative activity in leukemia cells are not fully understood. In this study, the apoptotic effects of DATS were investigated in human leukemia cells. Results Results of this study indicated that treatment with DATS resulted in significantly inhibited leukemia cell growth in a concentration- and time-dependent manner by induction of apoptosis. In U937 cells, DATS-induced apoptosis was correlated with down-regulation of Bcl-2, XIAP, and cIAP-1 protein levels, cleavage of Bid proteins, activation of caspases, and collapse of mitochondrial membrane potential. The data further demonstrated that DATS increased intracellular reactive oxygen species (ROS generation, which was attenuated by pretreatment with antioxidant N-acetyl-l-cysteine (NAC, a scavenger of ROS. In addition, administration of NAC resulted in significant inhibition of DATS-induced apoptosis by inhibiting activation of caspases. Conclusions The present study reveals that the cytotoxicity caused by DATS is mediated by generation of ROS and subsequent activation of the ROS-dependent caspase pathway in U937 leukemia cells.

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

    Science.gov (United States)

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

    2014-09-01

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

  5. Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats.

    Science.gov (United States)

    Kojima, Ryosuke; Takakura, Hideo; Kamiya, Mako; Kobayashi, Eiji; Komatsu, Toru; Ueno, Tasuku; Terai, Takuya; Hanaoka, Kenjiro; Nagano, Tetsuo; Urano, Yasuteru

    2015-12-01

    A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3 H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes. PMID:26474404

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

    Science.gov (United States)

    Sun, Qingrui; Chen, Tongsheng

    2009-02-01

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

  7. Electron spin resonance spectroscopy for the study of nanomaterial-mediated generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Weiwei He

    2014-03-01

    Full Text Available Many of the biological applications and effects of nanomaterials are attributed to their ability to facilitate the generation of reactive oxygen species (ROS. Electron spin resonance (ESR spectroscopy is a direct and reliable method to identify and quantify free radicals in both chemical and biological environments. In this review, we discuss the use of ESR spectroscopy to study ROS generation mediated by nanomaterials, which have various applications in biological, chemical, and materials science. In addition to introducing the theory of ESR, we present some modifications of the method such as spin trapping and spin labeling, which ultimately aid in the detection of short-lived free radicals. The capability of metal nanoparticles in mediating ROS generation and the related mechanisms are also presented.

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

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Paes

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Okada Futoshi

    2005-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Kurt J. Schillinger; Vickas V. Patel

    2012-01-01

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

  11. Crosstalk of reactive oxygen species and NF-κB signaling

    Institute of Scientific and Technical Information of China (English)

    Michael J Morgan; Zheng-gang Liu

    2011-01-01

    NF-κB proteins are a family of transcription factors that are of central importance in inflammation and immunity.NF-κB also plays important roles in other processes,including development,cell growth and survival,and proliferation,and is involved in many pathological conditions.Reactive Oxygen Species(ROS)are created by a variety of cellular processes as part of cellular signaling events.While certain NF-κB-regulated genes play a major role in regulating the amount of ROS in the cell,ROS have various inhibitory or stimulatory roles in NF-κB signaling.Here we review the regulation of ROS levels by NF-κB targets and various ways in which ROS have been proposed to impact NF-κB signaling pathways.

  12. Reactive oxygen species (ROS)-induced actin glutathionylation controls actin dynamics in neutrophils

    Science.gov (United States)

    Sakai, Jiro; Li, Jingyu; Subramanian, Kulandayan K.; Mondal, Subhanjan; Bajrami, Besnik; Hattori, Hidenori; Jia, Yonghui; Dickinson, Bryan C.; Zhong, Jia; Ye, Keqiang; Chang, Christopher J; Ho, Ye-Shih; Zhou, Jun; Luo, Hongbo R.

    2012-01-01

    Summary The regulation of actin dynamics is pivotal for cellular processes such as cell adhesion, migration, and phagocytosis, and thus is crucial for neutrophils to fulfill their roles in innate immunity. Many factors have been implicated in signal-induced actin polymerization, however the essential nature of the potential negative modulators are still poorly understood. Here we report that NADPH oxidase-dependent physiologically generated reactive oxygen species (ROS) negatively regulate actin polymerization in stimulated neutrophils via driving reversible actin glutathionylation. Disruption of glutaredoxin 1 (Grx1), an enzyme that catalyzes actin deglutathionylation, increased actin glutathionylation, attenuated actin polymerization, and consequently impaired neutrophil polarization, chemotaxis, adhesion, and phagocytosis. Consistently, Grx1-deficient murine neutrophils showed impaired in vivo recruitment to sites of inflammation and reduced bactericidal capability. Together, these results present a physiological role for glutaredoxin and ROS- induced reversible actin glutathionylation in regulation of actin dynamics in neutrophils. PMID:23159440

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Liangdong Hu

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Jie Qu

    2016-01-01

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

  17. Bistability of mitochondrial respiration underlies paradoxical reactive oxygen species generation induced by anoxia.

    Directory of Open Access Journals (Sweden)

    Vitaly A Selivanov

    2009-12-01

    Full Text Available Increased production of reactive oxygen species (ROS in mitochondria underlies major systemic diseases, and this clinical problem stimulates a great scientific interest in the mechanism of ROS generation. However, the mechanism of hypoxia-induced change in ROS production is not fully understood. To mathematically analyze this mechanism in details, taking into consideration all the possible redox states formed in the process of electron transport, even for respiratory complex III, a system of hundreds of differential equations must be constructed. Aimed to facilitate such tasks, we developed a new methodology of modeling, which resides in the automated construction of large sets of differential equations. The detailed modeling of electron transport in mitochondria allowed for the identification of two steady state modes of operation (bistability of respiratory complex III at the same microenvironmental conditions. Various perturbations could induce the transition of respiratory chain from one steady state to another. While normally complex III is in a low ROS producing mode, temporal anoxia could switch it to a high ROS producing state, which persists after the return to normal oxygen supply. This prediction, which we qualitatively validated experimentally, explains the mechanism of anoxia-induced cell damage. Recognition of bistability of complex III operation may enable novel therapeutic strategies for oxidative stress and our method of modeling could be widely used in systems biology studies.

  18. Amyloid-β and α-synuclein decrease the level of metal-catalyzed reactive oxygen species by radical scavenging and redox silencing

    DEFF Research Database (Denmark)

    Pedersen, Jeppe Trudslev; Chen, Serene W.; Borg, Christian Bernsen;

    2016-01-01

    The formation of reactive oxygen species (ROS) is linked to the pathogenesis of Alzheimer's and Parkinson's diseases. Here we have investigated the effect of soluble and aggregated Aβ and α-synuclein, associated with Alzheimer's and Parkinson's disease respectively, on the Cu2+-catalyzed formation......-active metal ions in the aggregates or as a downstream consequence of the formation of the patho-logical amyloid structures....

  19. Oxidation of Fatty Acids Is the Source of Increased Mitochondrial Reactive Oxygen Species Production in Kidney Cortical Tubules in Early Diabetes

    OpenAIRE

    Rosca, Mariana G.; Vazquez, Edwin J.; Chen, Qun; Kerner, Janos; Kern, Timothy S.; Hoppel, Charles L.

    2012-01-01

    Mitochondrial reactive oxygen species (ROS) cause kidney damage in diabetes. We investigated the source and site of ROS production by kidney cortical tubule mitochondria in streptozotocin-induced type 1 diabetes in rats. In diabetic mitochondria, the increased amounts and activities of selective fatty acid oxidation enzymes is associated with increased oxidative phosphorylation and net ROS production with fatty acid substrates (by 40% and 30%, respectively), whereas pyruvate oxidation is decr...

  20. Reactive oxygen species' role in endothelial dysfunction by electron paramagnetic resonance

    Science.gov (United States)

    Wassall, Cynthia D.

    The endothelium is a single layer of cells lining the arteries and is involved in many physiological reactions which are responsible for vascular tone. Free radicals are important participants in these chemical reactions in the endothelium. Here we quantify free radicals, ex vivo, in biological tissue with continuous wave electron paramagnetic resonance (EPR). In all of the experiments in this thesis, we use a novel EPR spin trapping technique that has been developed for tissue segments. EPR spin trapping is often considered the 'gold standard' in reactive oxygen species (ROS) detection because of its sensitivity and non-invasive nature. In all experiments, tissue was placed in physiological saline solution with 190-mM PBN (N-tert -butyl-α-phenylnitrone), 10% by volume dimethyl-sulphoxide (DMSO) for cryopreservation, and incubated in the dark for between 30 minutes up to 2 hours at 37°C while gently being stirred. Tissue and supernatant were then loaded into a syringe and frozen at -80°C until EPR analysis. In our experiments, the EPR spectra were normalized with respect to tissue volume. Conducting experiments at liquid nitrogen temperature leads to some experimental advantages. The freezing of the spin adducts renders them stable over a longer period, which allows ample time to analyze tissue samples for ROS. The dielectric constant of ice is greatly reduced over its liquid counterpart; this property of water enables larger sample volumes to be inserted into the EPR cavity without overloading it and leads to enhanced signal detection. Due to Maxwell-Boltzmann statistics, the population difference goes up as the temperature goes down, so this phenomenon enhances the signal intensity as well. With the 'gold standard' assertion in mind, we investigated whether slicing tissue to assay ROS that is commonly used in fluorescence experiments will show more free radical generation than tissue of a similar volume that remains unsliced. Sliced tissue exhibited a 76

  1. Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules

    Science.gov (United States)

    Kimyon, Önder; Das, Theerthankar; Ibugo, Amaye I.; Kutty, Samuel K.; Ho, Kitty K.; Tebben, Jan; Kumar, Naresh; Manefield, Mike

    2016-01-01

    Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms. PMID:27446013

  2. Serratia secondary metabolite prodigiosin inhibit Pseudomonas aeruginosa biofilm development by producing reactive oxygen species that damage biological molecules.

    Directory of Open Access Journals (Sweden)

    Onder eKimyon

    2016-06-01

    Full Text Available Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 µM (extracted from Serratia marcescens culture and a prodigiosin/copper(II (100 µM each complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosin to cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms.

  3. (Gold core)/(titania shell) nanostructures for plasmon-enhanced photon harvesting and generation of reactive oxygen species

    KAUST Repository

    Fang, Caihong

    2014-01-01

    Integration of gold and titania in a nanoscale core/shell architecture can offer large active metal/semiconductor interfacial areas and avoid aggregation and reshaping of the metal nanocrystal core. Such hybrid nanostructures are very useful for studying plasmon-enhanced/enabled processes and have great potential in light-harvesting applications. Herein we report on a facile route to (gold nanocrystal core)/(titania shell) nanostructures with their plasmon band synthetically variable from ∼700 nm to over 1000 nm. The coating method has also been applied to other mono- and bi-metallic Pd, Pt, Au nanocrystals. The gold/titania nanostructures have been employed as the scattering layer in dye-sensitized solar cells, with the resultant cells exhibiting a 13.3% increase in the power conversion efficiency and a 75% decrease in the scattering-layer thickness. Moreover, under resonant excitation, the gold/titania nanostructures can efficiently utilize low-energy photons to generate reactive oxygen species, including singlet oxygen and hydroxyl radicals.

  4. Production and Characterization of Active Transparent PET Films for Oxygen Sensitive Foods Packaging

    Science.gov (United States)

    Rosaria Galdi, Maria; Incarnato, Loredana

    2010-06-01

    The aim of this work is to investigate possible solutions to realize active, transparent PET film suitable for packaging oxygen sensitive foods. At this purpose, monolayer active PET films at different oxygen scavenger concentrations and multilayer active ones were produced by cast extrusion laboratory scale equipments. To assess their activity and to verify the efficacy of such solutions, O2 absorption analyses were carried out in continuous by an innovative oxygen meter.

  5. Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

    Science.gov (United States)

    Carpenter, Laurie Jean

    When administered intravenously or intratracheally to rats, rabbits and sheep, phorbol myristate acetate (PMA) produces changes in lung morphology and function are similar to those seen in humans with the adult respiratory distress syndrome (ARDS). Therefore, it is thought that information about the mechanism of ARDS development can be gained from experiments using PMA-treated animals. Currently, the mechanisms by which PMA causes pneumotoxicity are unknown. Results from other studies in rabbits and in isolated, perfused rabbit lungs suggest that PMA-induced lung injury is mediated by active oxygen species from neutrophils (PMN), whereas studies in sheep and rats suggest that PMN are not required for the toxic response. The role of PMN, active oxygen metabolites and thromboxane (TxA_2) in PMA-induced injury to isolated, perfused rat lungs (IPLs) was examined in this thesis. To determine whether PMN were required for PMA to produce toxicity to the IPL, lungs were perfused for 30 min with buffer containing various concentrations of PMA (in the presence or absence of PMN). When concentrations >=q57 ng/ml were added to medium devoid of added PMN, perfusion pressure and lung weight increased. When a concentration of PMA (14-28 ng/ml) that did not by itself cause lungs to accumulate fluid was added to the perfusion medium containing PMN (1 x 10 ^8), perfusion pressure increased, and lungs accumulated fluid. These results indicate that high concentrations of PMA produce lung injury which is independent of PMN, whereas injury induced by lower concentrations is PMN-dependent. To examine whether active oxygen species were involved in mediating lung injury induced by PMA and PMN, lungs were coperfused with the oxygen radical scavengers SOD and/or catalase. Coperfusion with either or both of these enzymes totally protected lungs against injury caused by PMN and PMA. These results suggest that active oxygen species (the hydroxyl radical in particular), mediate lung injury in

  6. Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies.Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease.

  7. Microcystin-LR induced reactive oxygen species mediate cytoskeletal disruption and apoptosis of hepatocytes in Cyprinus carpio L.

    Directory of Open Access Journals (Sweden)

    Jinlin Jiang

    Full Text Available Microcystins (MCs are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR contains Leucine (L and Arginine (R in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A activities and induce excessive production of reactive oxygen species (ROS. The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L. remains largely unclear. In our present study, the hydroxyl radical (•OH was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12-48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity.

  8. Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity.

    Science.gov (United States)

    Long, Thomas C; Saleh, Navid; Tilton, Robert D; Lowry, Gregory V; Veronesi, Bellina

    2006-07-15

    Concerns with the environmental and health risk of widely distributed, commonly used nanoparticles are increasing. Nanosize titanium dioxide (TiO2) is used in air and water remediation and in numerous products designed for direct human use and consumption. Its effectiveness in deactivating pollutants and killing microorganisms relates to photoactivation and the resulting free radical activity. This property, coupled with its multiple potential exposure routes, indicates that nanosize TiO2 could pose a risk to biological targets that are sensitive to oxidative stress damage (e.g., brain). In this study, brain microglia (BV2) were exposed to a physicochemically characterized (i.e., dispersion stability, particle size distribution, and zeta potential) nanomaterial, Degussa P25, and cellular expressions of reactive oxygen species were measured with fluorescent probes. P25's zeta potentials, measured in cell culture media and physiological buffer were -11.6 +/- 1.2 mV and -9.25 +/- 0.73 mV, respectively. P25 aggregation was rapid in both media and buffer with the hydrodynamic diameter of stable P25 aggregates ranging from 826 nm to 2368 nm depending on the concentration. The biological response of BV2 microglia to noncytotoxic (2.5-120 ppm) concentrations of P25 was a rapid (<5 min) and sustained (120 min) release of reactive oxygen species. The time course of this release suggested that P25 not only stimulated the immediate "oxidative burst" response in microglia but also interfered with mitochondrial energy production. Transmission electron microscopy indicated that small groups of nanosized particles and micron-sized aggregates were engulfed bythe microglia and sequestered as intracytoplasmic aggregates after 6 and 18 h exposure to P25 (2.5 ppm). Cell viability was maintained at all test concentrations (2.5-120 ppm) over the 18 h exposure period. These data indicate that mouse microglia respond to Degussa P25 with cellular and morphological expressions of free

  9. Effect of oxygen on the microbial activities of thermophilic anaerobic biomass.

    Science.gov (United States)

    Pedizzi, C; Regueiro, L; Rodriguez-Verde, I; Lema, J M; Carballa, M

    2016-07-01

    Low oxygen levels (μgO2L(-1)) in anaerobic reactors are quite common and no relevant consequences are expected. On the contrary, higher concentrations could affect the process. This work aimed to study the influence of oxygen (4.3 and 8.8mgO2L(-1), respectively) on the different microbial activities (hydrolytic, acidogenic and methanogenic) of thermophilic anaerobic biomass and on the methanogenic community structure. Batch tests in presence of oxygen were conducted using specific substrates for each biological activity and a blank (with minimum oxygen) was included. No effect of oxygen was observed on the hydrolytic and acidogenic activities. In contrast, the methane production rate decreased by 40% in all oxygenated batches and the development of active archaeal community was slower in presence of 8.8mgO2L(-1). However, despite this sensitivity of methanogens to oxygen at saturation levels, the inhibition was reversible. PMID:27020398

  10. Bleaching in coral reef anthozoans: effects of irradiance, ultraviolet radiation, and temperature on the activities of protective enzymes against active oxygen

    Science.gov (United States)

    Lesser, M. P.; Stochaj, W. R.; Tapley, D. W.; Shick, J. M.

    1990-04-01

    Recent widespread bleaching of coral reef anthozoans has been observed on the Great Barrier Reef, the Pacific coast of Panama, and in the Caribbean Sea. Bleaching events have been correlated with anomalously high sea surface temperatures which are presumed to cause the expulsion of zooxanthellae from their hosts. Our experimental results show that increases in temperature significantly reduce the total number of zooxanthellae per polyp. At the same time temperature, irradiance (photosynthetically active radiation=PAR), and ultraviolet radiation (UV) independently increase the activities of the enzymes superoxide dismutase, catalase, and ascorbate peroxidase within the zooxanthellae of the zoanthid Palythoa caribaeorum. Enzyme activities within the host are only suggestive of similar changes. These enzymes are responsible for detoxifying active forms of oxygen, and their elevated activities indirectly indicate an increase in the production of active oxygen species by increases in these environmental factors. Historically, bleaching has been attributed to changes in temperature, salinity, and UV. Increases in temperature or highly energetic UV radiation can increase the flux of active forms of oxygen, particularly at the elevated oxygen concentrations that prevail in the tissues during photosynthesis, with oxygen toxicity potentially mediating the bleaching event. Additionally, the concentration of UV absorbing compounds within the symbiosis is inversely related to temperature, potentially increasing exposure of the host and zooxanthellae to the direct effects of UV.

  11. Detection of oxygen species generated by WO3 modification fullerene/TiO2 in the degradation of 1,5-diphenyl carbazide

    International Nuclear Information System (INIS)

    Highlights: • Reactive oxygen species were detected through oxidation reaction from DPCI to DPCO. • Generated reactive oxygen species and hydroxyl radicals can be analysed by DPCI degradation. • C60 have good effect in photo/ultrasonic degradation process. • Enhanced adsorption capacity can increase the degradation effect. • Photocatalytic activity attributed to photo-absorption effect by C60 and cooperative effect of WO3 and TiO2. - Abstract: In the present work, powders with different relative mole ratios of WO3-fullerene/TiO2 were irradiated by visible light and ultrasonic. The composite obtained was characterized by BET surface area measurements, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), fourier transform infrared (FT-IR), transmission electron microscopy (TEM) and UV–vis analysis. A methylene blue (MB) solution under visible light and ultrasonic irradiation was used to determine the catalytic activity. The generation of reactive oxygen species were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). Finally, we performed experiments to find the optimum relative mole ratio of fullerene for the degradation of MB

  12. C-H bond activation by metal-superoxo species: what drives high reactivity?

    Science.gov (United States)

    Ansari, Azaj; Jayapal, Prabha; Rajaraman, Gopalan

    2015-01-01

    Metal-superoxo species are ubiquitous in metalloenzymes and bioinorganic chemistry and are known for their high reactivity and their ability to activate inert C-H bonds. The comparative oxidative abilities of M-O2(.-) species (M = Cr(III), Mn(III), Fe(III), and Cu(II)) towards C-H bond activation reaction are presented. These superoxo species generated by oxygen activation are found to be aggressive oxidants compared to their high-valent metal-oxo counterparts generated by O⋅⋅⋅O bond cleavage. Our calculations illustrate the superior oxidative abilities of Fe(III)- and Mn(III)-superoxo species compared to the others and suggest that the reactivity may be correlated to the magnetic exchange parameter.

  13. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma.

    Science.gov (United States)

    Rizvi, Asim; Farhan, Mohd; Naseem, Imrana; Hadi, S M

    2016-09-01

    Calcitriol is the metabolically active form of Vitamin D and is known to kill cancer cells. Using the rat model of DEN induced hepatocellular carcinoma we show that there is a marked increase in cellular levels of copper in hepatocellular carcinoma and that calcitriol-copper interaction leads to reactive oxygen species mediated DNA breakage selectively in hepatocellular carcinoma cells. In vivo studies show that calcitriol selectively induces severe fluctuations in cellular enzymatic and non enzymatic scavengers of reactive oxygen species in the malignant tissue. Lipid peroxidation, a well established marker of oxidative stress, was found to increase, and substantial cellular DNA breakage was observed. We propose that calcitriol is a proxidant in the cellular milieu of hepatocellular carcinoma cells, and this copper mediated prooxidant action of calcitriol causes selective DNA breakage in malignant cells, while sparing normal (non malignant) cells. PMID:27343126

  14. Influence of particle size and reactive oxygen species on cobalt chrome nanoparticle-mediated genotoxicity.

    Science.gov (United States)

    Raghunathan, Vijay Krishna; Devey, Michael; Hawkins, Sue; Hails, Lauren; Davis, Sean A; Mann, Stephen; Chang, Isaac T; Ingham, Eileen; Malhas, Ashraf; Vaux, David J; Lane, Jon D; Case, Charles P

    2013-05-01

    Patients with cobalt chrome (CoCr) metal-on-metal (MOM) implants may be exposed to a wide size range of metallic nanoparticles as a result of wear. In this study we have characterised the biological responses of human fibroblasts to two types of synthetically derived CoCr particles [(a) from a tribometer (30 nm) and (b) thermal plasma technology (20, 35, and 80 nm)] in vitro, testing their dependence on nanoparticle size or the generation of oxygen free radicals, or both. Metal ions were released from the surface of nanoparticles, particularly from larger (80 nm) particles generated by thermal plasma technology. Exposure of fibroblasts to these nanoparticles triggered rapid (2 h) generation of reactive oxygen species (ROS) that could be eliminated by inhibition of NADPH oxidase, suggesting that it was mediated by phagocytosis of the particles. The exposure also caused a more prolonged, MitoQ sensitive production of ROS (24 h), suggesting involvement of mitochondria. Consequently, we recorded elevated levels of aneuploidy, chromosome clumping, fragmentation of mitochondria and damage to the cytoskeleton particularly to the microtubule network. Exposure to the nanoparticles resulted in misshapen nuclei, disruption of mature lamin B1 and increased nucleoplasmic bridges, which could be prevented by MitoQ. In addition, increased numbers of micronuclei were observed and these were only partly prevented by MitoQ, and the incidence of micronuclei and ion release from the nanoparticles were positively correlated with nanoparticle size, although the cytogenetic changes, modifications in nuclear shape and the amount of ROS were not. These results suggest that cells exhibit diverse mitochondrial ROS-dependent and independent responses to CoCr particles, and that nanoparticle size and the amount of metal ion released are influential.

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

    Directory of Open Access Journals (Sweden)

    Kwang-Chul Kwon

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

  16. Reactive oxygen species prevent imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function.

    Directory of Open Access Journals (Sweden)

    Hyung-Ran Kim

    Full Text Available Psoriasis is a chronic inflammatory skin disease resulting from immune dysregulation. Regulatory T cells (Tregs are important in the prevention of psoriasis. Traditionally, reactive oxygen species (ROS are known to be implicated in the progression of inflammatory diseases, including psoriasis, but many recent studies suggested the protective role of ROS in immune-mediated diseases. In particular, severe cases of psoriasis vulgaris have been reported to be successfully treated by hyperbaric oxygen therapy (HBOT, which raises tissue level of ROS. Also it was reported that Treg function was closely associated with ROS level. However, it has been only investigated in lowered levels of ROS so far. Thus, in this study, to clarify the relationship between ROS level and Treg function, as well as their role in the pathogenesis of psoriasis, we investigated imiquimod-induced psoriatic dermatitis (PD in association with Treg function both in elevated and lowered levels of ROS by using knockout mice, such as glutathione peroxidase-1(-/- and neutrophil cytosolic factor-1(-/- mice, as well as by using HBOT or chemicals, such as 2,3-dimethoxy-1,4-naphthoquinone and N-acetylcysteine. The results consistently showed Tregs were hyperfunctional in elevated levels of ROS, whereas hypofunctional in lowered levels of ROS. In addition, imiquimod-induced PD was attenuated in elevated levels of ROS, whereas aggravated in lowered levels of ROS. For the molecular mechanism that may link ROS level and Treg function, we investigated the expression of an immunoregulatory enzyme, indoleamine 2,3-dioxygenase (IDO which is induced by ROS, in PD lesions. Taken together, it was implied that appropriately elevated levels of ROS might prevent psoriasis through enhancing IDO expression and Treg function.

  17. Induction of Heat Resistance in Wheat Coleoptiles by 4-Hydroxybenzoic Acid: Connection with the Generation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Yastreb T.O.

    2012-08-01

    Full Text Available The effect of 4-hydroxybenzoic acid (4-HBA on resistance of coleoptiles of 4-day-old etiolated seedlings of wheat (Triticum aestivum L., cv. Elegiya to damaging heating (10 min at 43°C and possible dependence of this effect on changes in the activities of enzymes producing and scavenging reactive oxygen species (ROS were investigated. Treatment of coleoptiles with 10 μM 4-HBA resulted in enhancing of superoxide anion-radical generation and maintaining of hydrogen peroxide content there in. Increasing of the rate of ROS production was significantly suppressed by inhibitors of NADPH oxidase (α-naphthol and peroxidase (salicylhydroxamic acid. Under the influence of 4-HBA the activities of superoxide dismutase and apoplastic forms of peroxidase were increased. The activity of oxalate oxidase and catalase has not changed. Exogenous 4-HBA improved coleoptiles heat resistance and its effects were comparable with the influence of salicylic acid. Antioxidant agent BHT (butylhydroxytoluene, inhibitors of NADPH oxidase and peroxidase significantly reduced the increasing of wheat coleoptiles heat resistance, caused by 4-HBA action. It was concluded that 4-HBA influence on coleoptiles heat resistance is realized with the ROS mediation.

  18. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species.

    Directory of Open Access Journals (Sweden)

    Hengjie Yuan

    Full Text Available Piperlongumine (PL is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known.We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen.PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect.PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.

  19. Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues.

    Science.gov (United States)

    Kondo, Yoshitaka; Sakuma, Rui; Ichisawa, Megumi; Ishihara, Katsuyuki; Kubo, Misako; Handa, Setsuko; Mugita, Hiroyuki; Maruyama, Naoki; Koga, Hidenori; Ishigami, Akihito

    2014-09-24

    Potato chips (PC) contain abundant amounts of the free radical scavenger ascorbic acid (AA) due to the rapid dehydration of potato tubers (Solanum tuberosum) that occurs during frying. To evaluate the antioxidant activity of PC, this study examined reactive oxygen species (ROS) levels in tissues from SMP30/GNL knockout (KO) mice that cannot synthesize AA and determined AA and ROS levels after the animals were fed 20 and 10% PC diets for 7 weeks. Compared with AA-sufficient mice, AA-depleted SMP30/GNL KO mice showed high ROS levels in tissues. SMP30/GNL KO mice fed a PC diet showed high AA and low ROS levels in the brain, heart, lung, testis, soleus muscle, plantaris muscle, stomach, small intestine, large intestine, eyeball, and epididymal fat compared with AA-depleted mice. The data suggest that PC intake increases AA levels and enhances ROS scavenging activity in tissues of SMP30/GNL KO mice, which are a promising model for evaluating the antioxidant activity of foods. PMID:25180784

  20. Electric and electrochemical properties of catalytically active oxygen electrode materials

    NARCIS (Netherlands)

    Burggraaf, A.J.; Dijk, van M.P.; Vries, de K.J.

    1986-01-01

    The electrical conductivity has been investigated of some oxygen ion and mixed conducting materials. Electrodes are prepared from thin sputtered layers of these oxides combined with a small Au or Pt strip. The kinetics of the oxygen reaction has been studied for temperatures of 820–1020 K and PO2 va

  1. Understanding Iron-based catalysts with efficient Oxygen reduction activity from first-principles calculations

    Science.gov (United States)

    Hafiz, Hasnain; Barbiellini, B.; Jia, Q.; Tylus, U.; Strickland, K.; Bansil, A.; Mukerjee, S.

    2015-03-01

    Catalysts based on Fe/N/C clusters can support the oxygen-reduction reaction (ORR) without the use of expensive metals such as platinum. These systems can also prevent some poisonous species to block the active sites from the reactant. We have performed spin-polarized calculations on various Fe/N/C fragments using the Vienna Ab initio Simulation Package (VASP) code. Some results are compared to similar calculations obtained with the Gaussian code. We investigate the partial density of states (PDOS) of the 3d orbitals near the Fermi level and calculate the binding energies of several ligands. Correlations of the binding energies with the 3d electronic PDOS's are used to propose electronic descriptors of the ORR associated with the 3d states of Fe. We also suggest a structural model for the most active site with a ferrous ion (Fe2+) in the high spin state or the so-called Doublet 3 (D3).

  2. Species specificity of resistance to oxygen diffusion in thin cuticular membranes from amphibious plants

    DEFF Research Database (Denmark)

    Frost-Christensen, Henning; Jørgensen, Lise Bolt; Floto, Franz

    2003-01-01

    oxygen, diffusion, cuticula, amphibious plants, Hygrophila, Berula, Lobelia, Mentha, Potamogeton, Veronica, aquatic plants, submerged plants......oxygen, diffusion, cuticula, amphibious plants, Hygrophila, Berula, Lobelia, Mentha, Potamogeton, Veronica, aquatic plants, submerged plants...

  3. Investigation on the reaction mechanisms of generation and loss of oxygen-related species in atmospheric-pressure pulsed dielectric barrier discharge in argon/oxygen mixture

    Science.gov (United States)

    Pan, Jie; Tan, Zhenyu; Pan, Guangsheng; Shan, Chunhong; Wang, Xiaolong; Liu, Yadi; Jiang, Jixiang

    2016-07-01

    This work presents a numerical investigation, using a 1-D fluid model, on the generation and loss of oxygen-related species and the spatial-temporal evolutions of the species densities in the atmospheric-pressure pulsed dielectric barrier discharge in the argon/oxygen mixture. The reaction pathways as well as their contributions to the generation and loss of oxygen-related species are given. The considered oxygen-related species include O, O(1D), O2(1Δg), O3, O+, O2+, O-, O2-, and O3-. The following significant results are obtained. O, O(1D), O2(1Δg), and O- are produced mainly via the electron impact with O2. Ar+ plays an essential role in the generation of O+ and O2+. Almost all of O3 derives from the reaction O2 + O2 + O → O3 + O2. The O3-related reactions produce an essential proportion of O2- and O3-. The substantial loss of O-, O2-, and O3- is induced by their reactions with O2+. Loss of O+, O, and O(1D) is mainly due to their reactions with O2, loss of O2(1Δg) due to O2(1Δg) impacts with O3 as well as the de-excitation reactions between O2(1Δg) and e, O2, and O, and loss of O3 due to the reactions between O3 and other neutral species. In addition, the densities of O+ and O(1D) present two obvious peaks at the pulse duration, but the densities of O2+, O, O2(1Δg), and O3 are almost unchanged. The densities of negative oxygen ions increase at the pulse duration and then decline. O- density is obviously large nearby the dielectric surfaces and the densities of O2- and O3- present generally uniform distributions.

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

    Directory of Open Access Journals (Sweden)

    Geoffry N De Iuliis

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

  5. Antioxidant Activity of Oxygen Evolving Enhancer Protein 1 Purified from Capsosiphon fulvescens.

    Science.gov (United States)

    Kim, Eun-Young; Choi, Youn Hee; Lee, Jung Im; Kim, In-Hye; Nam, Taek-Jeong

    2015-06-01

    This study was conducted to determine the antioxidant activity of a protein purified from Capsosiphon fulvescens. The purification steps included sodium acetate (pH 6) extraction and diethylaminoethyl-cellulose, reversed phase Shodex C4P-50 column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicated that the molecular weight of the purified protein was 33 kDa. The N-terminus and partial peptide amino acid sequence of this protein was identical to the sequence of oxygen evolving enhancer (OEE) 1 protein. The antioxidant activity of the OEE 1 was determined in vitro using a scavenging test with 4 types of reactive oxygen species (ROS), including the 2,2-diphenyl-1-picrylhydrazyl radical, hydroxyl radical, superoxide anion, and hydrogen peroxide (H2 O2 ). OEE 1 had higher H2 O2 scavenging activity, which proved to be the result of enzymatic antioxidants rather than nonenzymatic antioxidants. In addition, OEE 1 showed less H2 O2 -mediated ROS formation in HepG2 cells. In conclusion, this study demonstrates that OEE 1 purified from C. fulvescens is an excellent antioxidant. PMID:25944160

  6. Absorption spectroscopy of oxygen, carbon dioxide and water species for applications in combustion diagnostics

    Science.gov (United States)

    Mei, Anhua

    Laser absorption spectroscopy has been a useful tool applied in combustion diagnostics because of its capability to measure the species' concentration, particularly to measure concentration, temperature, and pressure simultaneously. These measurements provide the necessary information for dynamic combustion control. Due to its advantages such as fast response, non-intrusive nature and applicability under harsh environment like high temperature and high pressure, absorption laser spectroscopy makes it possible to monitor combustion system on-line and in situ. Since its development for more than thirty years, laser spectroscopy has matured, and the novel and advanced laser sensors have pushed it to be applied fast. On the other hand, industry still needs cheaper and more operable spectroscopy, which becomes an important consideration in the development and application of modern laser spectroscopy. This study presents an instrumental structure including the algorithm of the spectrum computation and the hardware configuration. The algorithm applied the central maximum value of the spectrum to simplify the computation. The whole calculation was done extensively using Beer-Lambert theory and HITRAN database which makes it efficient and applicable. This research conducted the simulations of high temperature species, such as CO2, H2O to carry out the algorithm, which were compared with published data. Also, this research designed and performed the experiments of measuring oxygen and its mixture with Helium by using a 760 nm diode laser and a 655 nm Helium/Neon laser sensor with fixed wavelength structures. The results of this research also conclude the following: (1) extensive literature survey, field research and laboratory work; (2) studying the significant theories and experimental methods of the laser spectroscopy; (3) developing efficient and simplified algorithm for spectrum calculation; (4) simulating high temperature species H2O and CO2; (5) designing and building

  7. Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty

    Directory of Open Access Journals (Sweden)

    Freeman Theresa A

    2009-11-01

    Full Text Available Abstract Background Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA, is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS and nitrogen species (RNS mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation. Results We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed in both macrophages and fibroblasts in arthrofibrotic tissue. As direct measurement of ROS/RNS is not feasible, products including DNA hydroxylation (8-OHdG, and protein nitrosylation (nitrotyrosine were measured by immunohistochemistry. Quantification of the staining showed that 8-OHdg was significantly increased in arthrofibrotic tissue. There was also a direct correlation between the intensity of inflammation and ROS/RNS to the amount of heterotopic ossification (HO. In order to investigate the aberrant expression of MPO, a real-time oxidative stress polymerase chain reaction array was performed on fibroblasts isolated from arthrofibrotic and control tissues. The results of this array confirmed the upregulation of MPO expression in arthrofibrotic fibroblasts and highlighted the downregulated expression of the antioxidants, superoxide dismutase1 and microsomal glutathione S-transferase 3, as well as the significant increase in thioredoxin reductase, a known promoter of cell proliferation, and polynucleotide kinase 3'-phosphatase, a key enzyme in the base excision repair pathway for oxidative DNA damage. Conclusion Based on our current findings, we suggest that ROS/RNS initiate and sustain the arthrofibrotic response driving

  8. Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

    Science.gov (United States)

    Recent studies with genetically modified mice and dietary antioxidants have suggested an important role for superoxide derived from NADPH oxidase (NOX) enzymes and other reactive oxygen species (ROS) such as hydrogen peroxide in regulation of normal bone turnover during development and also in the r...

  9. Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production

    NARCIS (Netherlands)

    Mathioudakis, D.; Engel, J.; Welters, I.D.; Dehne, M.G.; Matejec, R.; Harbach, H.; Henrich, M.; Schwandner, T.; Fuchs, M.; Weismuller, K.; Scheffer, G.J.; Muhling, J.

    2011-01-01

    For the first time the immunonutritional role of pyruvate on neutrophils (PMN), free alpha-keto and amino acid profiles, important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] as well as released myeloperoxidase (MPO) acitivity has been investiga

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

    U. Weyemi; B. Caillou; M. Talbot; R. Ameziane-El-Hassani; L. Lacroix; O. Lagent-Chevallier; A. Al Ghuzlan; D. Roos; J.M. Bidart; A. Virion; M. Schlumberger; C. Dupuy

    2010-01-01

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

  12. Trolox-sensitive reactive oxygen species regulate mitochondrial morphology, oxidative phosphorylation and cytosolic calcium handling in healthy cells

    NARCIS (Netherlands)

    Distelmaier, F.; Valsecchi, F.; Forkink, M.; Emst-de Vries, S.E. van; Swarts, H.G.P.; Rodenburg, R.J.T.; Verwiel, E.T.P.; Smeitink, J.A.M.; Willems, P.H.G.M.; Koopman, W.J.H.

    2012-01-01

    AIMS: Cell regulation by signaling reactive oxygen species (sROS) is often incorrectly studied through extracellular oxidant addition. Here, we used the membrane-permeable antioxidant Trolox to examine the role of sROS in mitochondrial morphology, oxidative phosphorylation (OXPHOS), and cytosolic ca

  13. Generation of Reactive Oxygen and Anti-Oxidant Species by Hydrodynamically-Stressed Suspensions of Morinda citrofolia

    Science.gov (United States)

    The generation of reactive oxygen species (ROS) by plant cell suspension cultures, in response to the imposition of both biotic and abiotic stress, is well-documented. This study investigated the generation of hydrogen peroxide by hydrodynamically-stressed cultures of Morinda citrifolia, over a 5-ho...

  14. Effect of reactive oxygen species (ROS) generating system for control of airborne microorganisms in meat processing environment

    Science.gov (United States)

    The effectiveness of reactive oxygen species (ROS) generating AirOcare equipment on the reduction of airborne bacteria in a meat processing environment was determined. Serratia marcescens and lactic acid bacteria (Lactococcus lactis subsp. lactis and Lactobacillus plantarum) were used to artificiall...

  15. REACTIVE OXYGEN SPECIES IN WHOLE BLOOD, BLOOD PLASMA AND BREAST MILK: VALIDATION OF A POTENTIAL MARKER OF EXPOSURE AND EFFECT

    Science.gov (United States)

    Reactive oxygen species (ROS) are recognized to contribute to the pathobiology of many diseases. We have applied a simple chemiluminescent (CL) probe to detect ROS in various biological fluids (plasma, whole blood, urine and breast milk) in an environmental arsenic drinking wate...

  16. Ingredients contribute to variation in production of reactive oxygen species by areca quid.

    Science.gov (United States)

    Chen, Ping-Ho; Tsai, Chi-Cheng; Lin, Ying-Chu; Ko, Ying-Chin; Yang, Yi-Hsin; Shieh, Tien-Yu; Ho, Pei-Shan; Li, Chien-Ming; Min-Shan Ko, Albert; Chen, Chung-Ho

    2006-06-01

    Areca quid (AQ) chewing has been implicated an independent risk factor for the development of oral cancer. Taiwanese areca quid (AQ) refers to a combination of areca nut (AN), lime, and inflorescence of Piper betle Linn. (IPB) or Piper betle leaf (PBL). Studies of AQ in other countries reported that AN extract combined with lime generates reactive oxygen species (ROS), such as hydroxyl radical (HO.), known to be a contributing factor in oral mucosa damage. To determine whether HO. is formed in the oral cavity during AQ chewing, the formation of meta-tyrosine (m-Tyr) and ortho-tyrosine (o-Tyr) from l-phenylalanine (Phe) was confirmed. It was demonstrated that combined aqueous extracts of AN, lime, metal ions (such as Cu2+ and Fe2+), and IPB or PBL produced HO.. Thus, the yield of HO. significantly increases when higher amounts of IPB or lime are added and also when Cu2+ and Fe2+ are increased. Further, the omission of any one of these ingredients significantly reduces the formation of HO.. Our results found that chewing AQ with IPB generated significantly higher HO. than chewing AQ with PBL, and may result in greater oxidative damage to the surrounding oral mucosa. PMID:16840253

  17. Hyperthermia, dehydration, and osmotic stress: unconventional sources of exercise-induced reactive oxygen species.

    Science.gov (United States)

    King, Michelle A; Clanton, Thomas L; Laitano, Orlando

    2016-01-15

    Evidence of increased reactive oxygen species (ROS) production is observed in the circulation during exercise in humans. This is exacerbated at elevated body temperatures and attenuated when normal exercise-induced body temperature elevations are suppressed. Why ROS production during exercise is temperature dependent is entirely unknown. This review covers the human exercise studies to date that provide evidence that oxidant and antioxidant changes observed in the blood during exercise are dependent on temperature and fluid balance. We then address possible mechanisms linking exercise with these variables that include shear stress, effects of hemoconcentration, and signaling pathways involving muscle osmoregulation. Since pathways of muscle osmoregulation are rarely discussed in this context, we provide a brief review of what is currently known and unknown about muscle osmoregulation and how it may be linked to oxidant production in exercise and hyperthermia. Both the circulation and the exercising muscle fibers become concentrated with osmolytes during exercise in the heat, resulting in a competition for available water across the muscle sarcolemma and other tissues. We conclude that though multiple mechanisms may be responsible for the changes in oxidant/antioxidant balance in the blood during exercise, a strong case can be made that a significant component of ROS produced during some forms of exercise reflect requirements of adapting to osmotic challenges, hyperthermia challenges, and loss of circulating fluid volume. PMID:26561649

  18. Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species.

    Science.gov (United States)

    Rebiger, Lars; Lenzen, Sigurd; Mehmeti, Ilir

    2016-01-21

    Brown adipose tissue (BAT) cells have a very high oxidative capacity. On the other hand, in obesity and obesity-related diabetes, levels of pro-inflammatory cytokines are elevated, which might promote BAT dysfunction and consequently impair carbohydrate metabolism and thereby exacerbate cellular dysfunction and promote diabetes progression. Therefore, the antioxidative enzyme status of a brown adipocyte cell line and its susceptibility towards pro-inflammatory cytokines, which participate in the pathogenesis of diabetes, and reactive oxygen species (ROS) were analysed. Mature brown adipocytes exhibited significantly higher levels of expression of mitochondrially and peroxisomally located antioxidative enzymes compared with non-differentiated brown adipocytes. Pro-inflammatory cytokines induced a significant decrease in the viability of differentiated brown adipocytes, which was accompanied by a massive ROS production and down-regulation of BAT-specific markers, such as uncoupling protein 1 (UCP-1) and β-Klotho. Taken together, the results strongly indicate that pro-inflammatory cytokines cause brown adipocyte dysfunction and death through suppression of BAT-specific proteins, especially of UCP-1 and β-Klotho, and consequently increased oxidative stress.

  19. Hydrogen Peroxide in Plants: a Versatile Molecule of the Reactive Oxygen Species Network

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Plants often face the challenge of severe environmental conditions, which include various biotic and abiotic stresses that exert adverse effects on plant growth and development. During evolution, plants have evolved complex regulatory mechanisms to adapt to various environmental stressors. One of the consequences of stress is an increase in the cellular concentration of reactive oxygen species (ROS), which are subsequently converted to hydrogen peroxide (H2O2). Even under normal conditions, higher plants produce ROS during metabolic processes. Excess concentrations of ROS result in oxidative damage to or the apoptotic death of cells. Development of an antioxidant defense system in plants protects them against oxidative stress damage. These ROS and, more particularly, H2O2, play versatile roles in normal plant physiological processes and in resistance to stresses. Recently, H2O2 has been regarded as a signaling molecule and regulator of the expression of some genes in cells. This review describes various aspects of H2O2 function, generation and scavenging,gene regulation and cross-links with other physiological molecules during plant growth, development and resistance responses.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-15

    Membrane bridges are key cellular structures involved in intercellular communication; however, dynamics for their formation are not well understood. We demonstrated the formation and regulation of novel extracellular ultrathin fibers in NIH3T3 cells using confocal and atomic force microscopy. At adjacent regions of neighboring cells, phorbol 12-myristate 13-acetate (PMA) and glucose oxidase induced ultrathin fiber formation, which was prevented by Trolox, a reactive oxygen species (ROS) scavenger. The height of ROS-sensitive ultrathin fibers ranged from 2 to 4 nm. PMA-induced formation of ultrathin fibers was inhibited by cytochalasin D, but not by Taxol or colchicine, indicating that ultrathin fibers mainly comprise microfilaments. PMA-induced ultrathin fibers underwent dynamic structural changes, resulting in formation of intercellular membrane bridges. Thus, these fibers are formed by a mechanism(s) involving ROS and involved in formation of intercellular membrane bridges. Furthermore, ultrastructural imaging of ultrathin fibers may contribute to understanding the diverse mechanisms of cell-to-cell communication and the intercellular transfer of biomolecules, including proteins and cell organelles.

  1. Ethylene response factor 6 is a regulator of reactive oxygen species signaling in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Nasser Sewelam

    Full Text Available Reactive oxygen species (ROS are produced in plant cells in response to diverse biotic and abiotic stresses as well as during normal growth and development. Although a large number of transcription factor (TF genes are up- or down-regulated by ROS, currently very little is known about the functions of these TFs during oxidative stress. In this work, we examined the role of ERF6 (ETHYLENE RESPONSE FACTOR6, an AP2/ERF domain-containing TF, during oxidative stress responses in Arabidopsis. Mutant analyses showed that NADPH oxidase (RbohD and calcium signaling are required for ROS-responsive expression of ERF6. erf6 insertion mutant plants showed reduced growth and increased H2O2 and anthocyanin levels. Expression analyses of selected ROS-responsive genes during oxidative stress identified several differentially expressed genes in the erf6 mutant. In particular, a number of ROS responsive genes, such as ZAT12, HSFs, WRKYs, MAPKs, RBOHs, DHAR1, APX4, and CAT1 were more strongly induced by H2O2 in erf6 plants than in wild-type. In contrast, MDAR3, CAT3, VTC2 and EX1 showed reduced expression levels in the erf6 mutant. Taken together, our results indicate that ERF6 plays an important role as a positive antioxidant regulator during plant growth and in response to biotic and abiotic stresses.

  2. The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies

    Directory of Open Access Journals (Sweden)

    Danina M. Muntean

    2016-01-01

    Full Text Available Ischaemia/reperfusion (I/R injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS. Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed.

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

    Science.gov (United States)

    Sewelam, Nasser; Kazan, Kemal; Schenk, Peer M

    2016-01-01

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

  4. Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species.

    Science.gov (United States)

    Han, Sang Jun; Jang, Hee-Seong; Kim, Jee In; Lipschutz, Joshua H; Park, Kwon Moo

    2016-02-29

    The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS).

  5. The angiotensin II-AT1 receptor stimulates reactive oxygen species within the cell nucleus

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    Pendergrass, Karl D.; Gwathmey, TanYa M. [The Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States); Michalek, Ryan D.; Grayson, Jason M. [Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157 (United States); Chappell, Mark C., E-mail: mchappel@wfubmc.edu [The Hypertension and Vascular Research Center, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2009-06-26

    We and others have reported significant expression of the Ang II Type 1 receptor (AT1R) on renal nuclei; thus, the present study assessed the functional pathways and distribution of the intracellular AT1R on isolated nuclei. Ang II (1 nM) stimulated DCF fluorescence, an intranuclear indicator of reactive oxygen species (ROS), while the AT1R antagonist losartan or the NADPH oxidase (NOX) inhibitor DPI abolished the increase in ROS. Dual labeling of nuclei with antibodies against nucleoporin 62 (Nup62) and AT1R or the NADPH oxidase isoform NOX4 revealed complete overlap of the Nup62 and AT1R (99%) by flow cytometry, while NOX4 was present on 65% of nuclei. Treatment of nuclei with a PKC agonist increased ROS while the PKC inhibitor GF109203X or PI3 kinase inhibitor LY294002 abolished Ang II stimulation of ROS. We conclude that the Ang II-AT1R-PKC axis may directly influence nuclear function within the kidney through a redox sensitive pathway.

  6. Mitochondrial uncoupling does not decrease reactive oxygen species production after ischemia-reperfusion.

    Science.gov (United States)

    Quarrie, Ricardo; Lee, Daniel S; Reyes, Levy; Erdahl, Warren; Pfeiffer, Douglas R; Zweier, Jay L; Crestanello, Juan A

    2014-10-01

    Cardiac ischemia-reperfusion (IR) leads to myocardial dysfunction by increasing production of reactive oxygen species (ROS). Mitochondrial H(+) leak decreases ROS formation; it has been postulated that increasing H(+) leak may be a mechanism of decreasing ROS production after IR. Ischemic preconditioning (IPC) decreases ROS formation after IR, but the mechanism is unknown. We hypothesize that pharmacologically increasing mitochondrial H(+) leak would decrease ROS production after IR. We further hypothesize that IPC would be associated with an increase in the rate of H(+) leak. Isolated male Sprague-Dawley rat hearts were subjected to either control or IPC. Mitochondria were isolated at end equilibration, end ischemia, and end reperfusion. Mitochondrial membrane potential (mΔΨ) was measured using a tetraphenylphosphonium electrode. Mitochondrial uncoupling was achieved by adding increasing concentrations of FCCP. Mitochondrial ROS production was measured by fluorometry using Amplex-Red. Pyridine dinucleotide levels were measured using HPLC. Before IR, increasing H(+) leak decreased mitochondrial ROS production. After IR, ROS production was not affected by increasing H(+) leak. H(+) leak increased at end ischemia in control mitochondria. IPC mitochondria showed no change in the rate of H(+) leak throughout IR. NADPH levels decreased after IR in both IPC and control mitochondria while NADH increased. Pharmacologically, increasing H(+) leak is not a method of decreasing ROS production after IR. Replenishing the NADPH pool may be a means of scavenging the excess ROS thereby attenuating oxidative damage after IR.

  7. (±)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes

    International Nuclear Information System (INIS)

    (±)-2-Chloropropionic acid (2-CPA) is a neurotoxic compound which kills cerebellar granule cells in vivo, and makes cerebellar granule cells in vitro produce reactive oxygen species (ROS). We have studied the effect of 2-CPA on ROS formation in human neutrophil granulocytes in vitro. We found an increased formation of ROS after 2-CPA exposure using three different methods; the fluorescent probe DCFH-DA and the chemiluminescent probes lucigenin and luminol. Four different inhibitors of ROS formation were tested on the cells in combination with 2-CPA to characterize the signalling pathways. The spin-trap s-PBN, the ERK1/2 inhibitor U0126 and the antioxidant Vitamin E inhibited the 2-CPA-induced ROS formation completely, while the mitochondrial transition permeability pore blocker cyclosporine A inhibited the ROS formation partly. We also found that 2-CPA induced an increased nitric oxide production in the cells by using the Griess reagent. The level of reduced glutathione, measured with the DTNB assay, was decreased after exposure to high concentrations of 2-CPA. Western blotting analysis showed that 2-CPA exposure led to an elevated phosphorylation of ERK MAP kinase. This phosphorylation was inhibited by U0126. Based on these experiments it seems like the mechanisms for 2-CPA induced toxicity involves ROS formation and is similar in neutrophil granulocytes as earlier shown in cerebellar granule cells. This also implies that 2-CPA may be immunotoxic

  8. Redox cycling and generation of reactive oxygen species in commercial infant formulas.

    Science.gov (United States)

    Boatright, William L; Crum, Andrea D

    2016-04-01

    Three nationally prominent commercial powdered infant formulas generated hydrogen peroxide, ranging from 10.46 to 11.62 μM, when prepared according to the manufacturer's instructions. Treating infant formulas with the chelating agent diethylene triamine pentaacetic acid (DTPA) significantly reduced H2O2 generation. In contrast, the addition of disodium ethylenediaminetetraacetic acid (EDTA) elevated the level of H2O2 generated in the same infant formulas by approximately 3- to 4-fold above the untreated infant formulas. The infant formulas contained ascorbate radicals ranging from about 138 nM to 40 nM. Treatment with catalase reduced the ascorbate radical contents by as much as 67%. Treatment with DTPA further reduced ascorbate radical signals to below quantifiable levels in most samples, further implicating the involvement of transition metal redox cycling in reactive oxygen species (ROS) formation. Supportive evidence of the generation of ROS is provided using luminol-enhanced luminescence (LEL) in both model mixtures of ascorbic acid and in commercial infant formulas.

  9. Autophagy induction upon reactive oxygen species in Cd-stressed Arabidopsis thaliana

    Science.gov (United States)

    Zhang, WeiNa; Chen, WenLi

    2010-02-01

    Autophagy is a protein degradation process in which cells recycle cytoplasmic contents when subjected to environmental stress conditions or during certain stages of development. Upon the induction of autophagy, a double membrane autophagosome forms around cytoplasmic components and delivers them to the vacuole for degradation. In plants, autophagy has been shown previously to be induced during abiotic stresses including oxidative stress. Cd, as a toxicity heavy metal, resulted in the production of reactive oxygen species (ROS). In this paper, we demonstrated that ROS contributed to the induction of autophagy in Cd-stressed Arabidopsis thaliana. However, pre-incubation with ascorbic acid (AsA, antioxidant molecule) and catalase (CAT, a H2O2-specific scavenger) decreased the ROS production and the number of autolysosomal-like structures. Together our results indicated that the oxidative condition was essential for autophagy, as treatment with AsA and CAT abolished the formation of autophagosomes, and ROS may function as signal molecules to induce autophagy in abiotic stress.

  10. Macrophage migration inhibitory factor induces autophagy via reactive oxygen species generation.

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    Yung-Chun Chuang

    Full Text Available Autophagy is an evolutionarily conserved catabolic process that maintains cellular homeostasis under stress conditions such as starvation and pathogen infection. Macrophage migration inhibitory factor (MIF is a multifunctional cytokine that plays important roles in inflammation and tumorigenesis. Cytokines such as IL-1β and TNF-α that are induced by MIF have been shown to be involved in the induction of autophagy. However, the actual role of MIF in autophagy remains unclear. Here, we have demonstrated that incubation of human hepatoma cell line HuH-7 cells with recombinant MIF (rMIF induced reactive oxygen species (ROS production and autophagy formation, including LC3-II expression, LC3 punctae formation, autophagic flux, and mitochondria membrane potential loss. The autophagy induced by rMIF was inhibited in the presence of MIF inhibitor, ISO-1 as well as ROS scavenger N-acetyl-L-cysteine (NAC. In addition, serum starvation-induced MIF release and autophagy of HuH-7 cells were partly blocked in the presence of NAC. Moreover, diminished MIF expression by shRNA transfection or inhibition of MIF by ISO-1 decreased serum starvation-induced autophagy of HuH-7 cells. Taken together, these data suggest that cell autophagy was induced by MIF under stress conditions such as inflammation and starvation through ROS generation.

  11. Direct effects of reactive oxygen species on cochlear outer hair cell shape in vitro.

    Science.gov (United States)

    Clerici, W J; DiMartino, D L; Prasad, M R

    1995-04-01

    Reactive oxygen species (ROS) have been implicated in the ototoxicity of various agents. This study examines the effects of superoxide anion (O2), hydroxyl radical (OH.) and hydrogen peroxide (H2O2), on isolated cochlear outer hair cell (OHC) morphology. OHCs were superfused with artificial perilymph (AP) or AP containing a specific ROS scavenger, and then with AP, ROS system or scavenger plus ROS system for 90 min. The generation of ROS as well as the scavenging properties of other agents were confirmed by specific biochemical assays. Control cells decreased 4.8% in mean length, and showed no obvious membrane damage. Generation of O2. or OH. resulted in high rates (85.7 and 42.9%, respectively) of bleb formation at the synaptic pole, and decreased (O2., 15.2%; OH., 17.3%) mean cell length. Length change and bleb formation rate were H2O2 concentration-dependent. 20 mM H2O2 led to 33.3% decreased mean cell length, and only 20% bleb formation; 0.1 mM H2O2 led to 83.3% bleb formation, with no length decrease. Superoxide dismutase, deferoxamine and catalase protected against O2., OH. and H2O2 effects, respectively. Bleb formation and diminished cell length likely represent differential lipid peroxidative outcomes at supra- and infranuclear membranes, and are consistent with effects of certain ototoxicants.

  12. Endogenous reactive oxygen species content and modulation of tyrosine phosphorylation during sperm capacitation.

    Science.gov (United States)

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