Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells

PubMed Central

Bauer, Georg

2015-01-01

Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of NO metabolism and direct catalase inhibitors. The latter aspect is explicitely studied for the interaction between catalase inhibiting acetylsalicylic acid and an NO donor. It is also shown that hybrid molecules like NO-aspirin utilize this synergistic potential. Our data open novel approaches for rational tumor therapy based on specific ROS signaling and its control in tumor cells. PMID:26342455

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

PubMed

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

2017-11-01

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

H2O2 generated from mitochondrial electron transport chain in thoracic perivascular adipose tissue is crucial for modulation of vascular smooth muscle contraction.

PubMed

Costa, Rafael M; Filgueira, Fernando P; Tostes, Rita C; Carvalho, Maria Helena C; Akamine, Eliana H; Lobato, Nubia S

2016-09-01

The perivascular adipose tissue (PVAT) releases a variety of factors that affect vascular function. PVAT in the thoracic aorta shares characteristics with the brown adipose tissue, including a large amount of mitochondria. PVAT-derived factors influence both endothelial and smooth muscle function via several signaling mechanisms including the release/generation of reactive nitrogen and oxygen species. Considering the importance of reactive oxygen species (ROS) on vascular function and that mitochondria are an important source of ROS, we hypothesized that mitochondria-derived ROS in the PVAT modulates vascular reactivity. Vascular reactivity to norephinephrine (NE) was evaluated in thoracic aortic rings, with or without endothelium and/or PVAT, from male Wistar rats. Mitochondrial uncoupling, as well as hydrogen peroxide (H2O2) removal, increased the contraction in vessels surrounded by PVAT. PVAT stimulated with NE exhibited increased protein expression, determined by Western blot analysis, of manganese superoxide dismutase (Mn-SOD) and decreased protein expression of catalase. Ultimately, NE increased superoxide anion (O2(-)) generation in PVAT via increases in intracellular calcium. These results clearly demonstrate that mitochondrial electron transport chain (mETC) in PVAT contributes to modulation of aortic muscle contraction by generating higher amounts of O2(-) that is, in turn, dismutated to hydrogen peroxide, which then acts as a pivotal signaling molecule regulating vascular smooth muscle contraction. Copyright © 2015 Elsevier Inc. All rights reserved.

Seed-vectored endophytic bacteria modulate development of rice seedlings.

PubMed

Verma, S K; Kingsley, K; Irizarry, I; Bergen, M; Kharwar, R N; White, J F

2017-06-01

The aim of the present study was to evaluate the effects of the removal of indigenous bacteria from rice seeds on seedling growth and development. Here we report the presence of three indigenous endophytic bacteria in rice seeds that play important roles in modulating seedling development (shoot and root lengths, and formation of root hairs and secondary roots) and defence against pathogens. Seed-associated bacteria were removed using surface sterilization with NaOCl (bleach) followed by antibiotic treatment. When bacteria were absent, growth of seedlings in terms of root hair development and overall seedling size was less than that of seedlings that contained bacteria. Reactive oxygen staining of seedlings showed that endophytic bacteria became intracellular in root parenchyma cells and root hairs. Roots containing endophytic bacteria were seen to stain densely for reactive oxygen, while roots free of bacteria stained lightly for reactive oxygen. Bacteria were isolated and identified as Enterobacter asburiae (VWB1), Pantoea dispersa (VWB2) and Pseudomonas putida (VWB3) by 16S rDNA sequencing. Bacteria were found to produce indole acetic acid (auxins), inhibited the pathogen Fusarium oxysporum and solubilized phosphate. Reinoculation of bacteria onto seedlings derived from surface-disinfected rice and Bermuda grass seeds significantly restored seedling growth and development. Rice seeds harbour indigenous bacterial endophytes that greatly influence seedling growth and development, including root and shoot lengths, root hair formation and disease susceptibility of rice seedlings. This study shows that seeds of rice naturally harbour bacterial endophytes that play key roles in modulation of seedling development. © 2017 The Society for Applied Microbiology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Ruiter, Graham; Carsch, Kurtis M.; Gul, Sheraz

In this paper, we report the synthesis, characterization, and reactivity of [LFe 3(PhPz) 3OMn( sPhIO)][OTf] x (3: x=2; 4: x=3), where 4 is one of very few examples of iodosobenzene–metal adducts characterized by X-ray crystallography. Access to these rare heterometallic clusters enabled differentiation of the metal centers involved in oxygen atom transfer (Mn) or redox modulation (Fe). Specifically, 57Fe Mössbauer and X-ray absorption spectroscopy provided unique insights into how changes in oxidation state (Fe III 2Fe IIMn II vs. Fe III 3Mn II) influence oxygen atom transfer in tetranuclear Fe 3Mn clusters. Finally, in particular, a one-electron redox change atmore » a distal metal site leads to a change in oxygen atom transfer reactivity by ca. two orders of magnitude.« less

Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia-reperfusion injury.

PubMed

Neeff, Hannes P; Sommer, Olaf; Meyer, Sebastian; Tinelli, Anja; Scholtes, Moritz; Hopt, Ulrich T; Drognitz, Oliver; von Dobschuetz, Ernst

2012-10-01

Reason for the unsuccessful use of antioxidants in transplantation might be the unknown kinetics of reactive oxygen species (ROS) release. In this study, we compared the kinetics of ROS release from rat pancreata in the presence and absence of blood. In vivo, ischemia-reperfusion injury (IRI) was induced in pancreata of male Wistar rats by occlusion of the arterial blood supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity, myeloperoxidase activity, and adenosine triphosphate content were measured. During reperfusion, an increase in IRI-induced ROS in arterial blood was noted after 2 hours of warm ischemia. In sharp contrast, ROS release was immediate and short lived in blood-free perfused organs. The degree of tissue damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase activity and adenosine triphosphate content. Antioxidative capacity of tissues was reduced. Electron spin resonance spectroscopy in conjunction with spin labels allows for the detection of ROS kinetics in pancreatic IRI. Reactive oxygen species kinetics are dependent on the length of the ischemic period and the presence or absence of blood.

Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells.

PubMed

Bauer, Georg

2015-12-01

Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of NO metabolism and direct catalase inhibitors. The latter aspect is explicitely studied for the interaction between catalase inhibiting acetylsalicylic acid and an NO donor. It is also shown that hybrid molecules like NO-aspirin utilize this synergistic potential. Our data open novel approaches for rational tumor therapy based on specific ROS signaling and its control in tumor cells. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Multifunctional albumin-MnO₂ nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response.

PubMed

Prasad, Preethy; Gordijo, Claudia R; Abbasi, Azhar Z; Maeda, Azusa; Ip, Angela; Rauth, Andrew Michael; DaCosta, Ralph S; Wu, Xiao Yu

2014-04-22

Insufficient oxygenation (hypoxia), acidic pH (acidosis), and elevated levels of reactive oxygen species (ROS), such as H2O2, are characteristic abnormalities of the tumor microenvironment (TME). These abnormalities promote tumor aggressiveness, metastasis, and resistance to therapies. To date, there is no treatment available for comprehensive modulation of the TME. Approaches so far have been limited to regulating hypoxia, acidosis, or ROS individually, without accounting for their interdependent effects on tumor progression and response to treatments. Hence we have engineered multifunctional and colloidally stable bioinorganic nanoparticles composed of polyelectrolyte-albumin complex and MnO2 nanoparticles (A-MnO2 NPs) and utilized the reactivity of MnO2 toward peroxides for regulation of the TME with simultaneous oxygen generation and pH increase. In vitro studies showed that these NPs can generate oxygen by reacting with H2O2 produced by cancer cells under hypoxic conditions. A-MnO2 NPs simultaneously increased tumor oxygenation by 45% while increasing tumor pH from pH 6.7 to pH 7.2 by reacting with endogenous H2O2 produced within the tumor in a murine breast tumor model. Intratumoral treatment with NPs also led to the downregulation of two major regulators in tumor progression and aggressiveness, that is, hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the tumor. Combination treatment of the tumors with NPs and ionizing radiation significantly inhibited breast tumor growth, increased DNA double strand breaks and cancer cell death as compared to radiation therapy alone. These results suggest great potential of A-MnO2 NPs for modulation of the TME and enhancement of radiation response in the treatment of cancer.

NQO2 Is a Reactive Oxygen Species Generating Off-Target for Acetaminophen

PubMed Central

2014-01-01

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. PMID:25313982

Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis.

PubMed

Dorighello, Gabriel G; Paim, Bruno A; Kiihl, Samara F; Ferreira, Mônica S; Catharino, Rodrigo R; Vercesi, Anibal E; Oliveira, Helena C F

2016-01-01

Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

Targeted modulation of reactive oxygen species in the vascular endothelium.

PubMed

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Interaction between neuronal nitric oxide synthase signaling and temperature influences sarcoplasmic reticulum calcium leak: role of nitroso-redox balance.

PubMed

Dulce, Raul A; Mayo, Vera; Rangel, Erika B; Balkan, Wayne; Hare, Joshua M

2015-01-02

Although nitric oxide (NO) signaling modulates cardiac function and excitation-contraction coupling, opposing results because of inconsistent experimental conditions, particularly with respect to temperature, confound the ability to elucidate NO signaling pathways. Here, we show that temperature significantly modulates NO effects. To test the hypothesis that temperature profoundly affects nitroso-redox equilibrium, thereby affecting sarcoplasmic reticulum (SR) calcium (Ca(2+)) leak. We measured SR Ca(2+) leak in cardiomyocytes from wild-type (WT), NO/redox imbalance (neuronal nitric oxide synthase-deficient mice-1 [NOS1(-/-)]), and hyper S-nitrosoglutathione reductase-deficient (GSNOR(-/-)) mice. In WT cardiomyocytes, SR Ca(2+) leak increased because temperature decreased from 37°C to 23°C, whereas in NOS1(-/-) cells, the leak suddenly increased when the temperature surpassed 30°C. GSNOR(-/-) cardiomyocytes exhibited low leak throughout the temperature range. Exogenously added NO had a biphasic effect on NOS1(-/-) cardiomyocytes; reducing leak at 37°C but increasing it at subphysiological temperatures. Oxypurinol and Tempol diminished the leak in NOS1(-/-) cardiomyocytes. Cooling from 37°C to 23°C increased reactive oxygen species generation in WT but decreased it in NOS1(-/-) cardiomyocytes. Oxypurinol further reduced reactive oxygen species generation. At 23°C in WT cells, leak was decreased by tetrahydrobiopterin, an essential NOS cofactor. Cooling significantly increased SR Ca(2+) content in NOS1(-/-) cells but had no effect in WT or GSNOR(-/-). Ca(2+) leak and temperature are normally inversely proportional, whereas NOS1 deficiency reverses this effect, increasing leak and elevating reactive oxygen species production because temperature increases. Reduced denitrosylation (GSNOR deficiency) eliminates the temperature dependence of leak. Thus, temperature regulates the balance between NO and reactive oxygen species which in turn has a major effect on SR Ca(2+). © 2014 American Heart Association, Inc.

Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress

PubMed Central

Lin, Abraham; Truong, Billy; Patel, Sohil; Kaushik, Nagendra; Choi, Eun Ha; Fridman, Gregory; Fridman, Alexander; Miller, Vandana

2017-01-01

A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. Secreted danger signals from cells undergoing immunogenic death enhanced the anti-tumor activity of macrophages. This study demonstrated that plasma triggers immunogenic cell death through oxidative stress pathways and highlights its potential development for cancer immunotherapy. PMID:28467380

[Oxygen and the superoxide anion. Modulation of NADPH oxidase?].

PubMed

Delbosc, S; Cristol, J P; Descomps, B; Chénard, J; Sirois, P

2001-01-01

Oxidative stress which results from an imbalance between oxidant production and antioxidant defense mechanisms can promote modifications of lipids, proteins and nucleic acids. This review focuses on the different pathways leading to Reactive Oxygen Species (ROS) production in particular on NADPH oxidase activation. This enzyme is localized in numerous cells including phagocytes and vascular cells and composed of membrane and cytosolic sub-units. The activation of the NADPH oxidase is largely involved in inflammation associated diseases such as asthma, Systemic Inflammatory Response Syndrome and aging associated diseases such as atherosclerosis and neurodeneratives diseases. The modulation of NADPH oxidase could be a way to limit or prevent the development of these diseases.

Antagonistic Basic Helix-Loop-Helix/bZIP Transcription Factors Form Transcriptional Modules That Integrate Light and Reactive Oxygen Species Signaling in Arabidopsis[W

PubMed Central

Chen, Dongqin; Xu, Gang; Tang, Weijiang; Jing, Yanjun; Ji, Qiang; Fei, Zhangjun; Lin, Rongcheng

2013-01-01

The critical developmental switch from heterotrophic to autotrophic growth of plants involves light signaling transduction and the production of reactive oxygen species (ROS). ROS function as signaling molecules that regulate multiple developmental processes, including cell death. However, the relationship between light and ROS signaling remains unclear. Here, we identify transcriptional modules composed of the basic helix-loop-helix and bZIP transcription factors PHYTOCHROME-INTERACTING FACTOR1 (PIF1), PIF3, ELONGATED HYPOCOTYL5 (HY5), and HY5 HOMOLOGY (HYH) that bridge light and ROS signaling to regulate cell death and photooxidative response. We show that pif mutants release more singlet oxygen and exhibit more extensive cell death than the wild type during Arabidopsis thaliana deetiolation. Genome-wide expression profiling indicates that PIF1 represses numerous ROS and stress-related genes. Molecular and biochemical analyses reveal that PIF1/PIF3 and HY5/HYH physically interact and coordinately regulate the expression of five ROS-responsive genes by directly binding to their promoters. Furthermore, PIF1/PIF3 and HY5/HYH function antagonistically during the seedling greening process. In addition, phytochromes, cryptochromes, and CONSTITUTIVE PHOTOMORPHOGENIC1 act upstream to regulate ROS signaling. Together, this study reveals that the PIF1/PIF3-HY5/HYH transcriptional modules mediate crosstalk between light and ROS signaling and sheds light on a new mechanism by which plants adapt to the light environments. PMID:23645630

Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.

PubMed Central

Hansen, J; Thomas, G D; Harris, S A; Parsons, W J; Victor, R G

1996-01-01

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity > 10% of maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC), contraction-induced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia. We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia. PMID:8755671

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

PubMed Central

Kvietys, Peter R.; Granger, D. Neil

2012-01-01

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

Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities

PubMed Central

Lubos, Edith; Loscalzo, Joseph

2011-01-01

Abstract Reactive oxygen species, such as superoxide and hydrogen peroxide, are generated in all cells by mitochondrial and enzymatic sources. Left unchecked, these reactive species can cause oxidative damage to DNA, proteins, and membrane lipids. Glutathione peroxidase-1 (GPx-1) is an intracellular antioxidant enzyme that enzymatically reduces hydrogen peroxide to water to limit its harmful effects. Certain reactive oxygen species, such as hydrogen peroxide, are also essential for growth factor-mediated signal transduction, mitochondrial function, and maintenance of normal thiol redox-balance. Thus, by limiting hydrogen peroxide accumulation, GPx-1 also modulates these processes. This review explores the molecular mechanisms involved in regulating the expression and function of GPx-1, with an emphasis on the role of GPx-1 in modulating cellular oxidant stress and redox-mediated responses. As a selenocysteine-containing enzyme, GPx-1 expression is subject to unique forms of regulation involving the trace mineral selenium and selenocysteine incorporation during translation. In addition, GPx-1 has been implicated in the development and prevention of many common and complex diseases, including cancer and cardiovascular disease. This review discusses the role of GPx-1 in these diseases and speculates on potential future therapies to harness the beneficial effects of this ubiquitous antioxidant enzyme. Antioxid. Redox Signal. 15, 1957–1997. PMID:21087145

Hyperglycemia and anthocyanin inhibit quercetin metabolism in HepG2 cells

USDA-ARS?s Scientific Manuscript database

A high glucose (Glu) milieu promotes generation of reactive oxygen species, which may not only cause cellular damage, but also modulate phase II enzymes that are responsible for the metabolism of flavonoids. Thus, we examined the effect of a high Glu milieu on quercetin (Q) metabolism in HepG2 cells...

Evolution of phenolic compounds and astringency during aging of red wine: effect of oxygen exposure before and after bottling.

PubMed

Gambuti, Angelita; Rinaldi, Alessandra; Ugliano, Maurizio; Moio, Luigi

2013-02-27

The aim of this study was to evaluate the effect of oxygen exposure of red wine, before (micro-oxygenation) and after (nano-oxygenation) bottling, on the phenolic composition and astringency of wine. The astringency was evaluated by sensory analysis and by a method based on the SDS-PAGE of salivary proteins after reaction of saliva with wine (SPI, saliva precipitation index). Micro-oxygenation caused a stabilization of color, but this effect disappeared after long aging. For the wine with the lower pH a decrease of wine astringency and SPI was observed 42 months after micro-oxygenation. Oxygen ingress through the closure postbottling was positively correlated with the decrease of SPI. Therefore, the astringency and reactivity of wines toward salivary proteins of a bottled red wine can be modulated by controlled oxygen exposure during aging. For both experiments the effect of oxygen exposure depended on wine composition.

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

PubMed Central

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

2017-01-01

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

Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez-de-Arce, Karen; Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago; Foncea, Rocio

2005-12-16

It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNAmore » and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.« less

Spin Biochemistry Modulates Reactive Oxygen Species (ROS) Production by Radio Frequency Magnetic Fields

PubMed Central

Usselman, Robert J.; Hill, Iain; Singel, David J.; Martino, Carlos F.

2014-01-01

The effects of weak magnetic fields on the biological production of reactive oxygen species (ROS) from intracellular superoxide (O2 •−) and extracellular hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial smooth muscle cells (rPASMC). A decrease in O2 •− and an increase in H2O2 concentrations were observed in the presence of a 7 MHz radio frequency (RF) at 10 μTRMS and static 45 μT magnetic fields. We propose that O2 •− and H2O2 production in some metabolic processes occur through singlet-triplet modulation of semiquinone flavin (FADH•) enzymes and O2 •− spin-correlated radical pairs. Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that presumably decouple flavin hyperfine interactions during spin coherence. RF flavin hyperfine decoupling results in an increase of H2O2 singlet state products, which creates cellular oxidative stress and acts as a secondary messenger that affects cellular proliferation. This study demonstrates the interplay between O2 •− and H2O2 production when influenced by RF magnetic fields and underscores the subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth. PMID:24681944

Differential modulation of ROS signals and other mitochondrial parameters by the antioxidants MitoQ, resveratrol and curcumin in human adipocytes.

PubMed

Hirzel, Estelle; Lindinger, Peter W; Maseneni, Swarna; Giese, Maria; Rhein, Véronique Virginie; Eckert, Anne; Hoch, Matthias; Krähenbühl, Stephan; Eberle, Alex N

2013-10-01

Mitochondrial reactive oxygen species (ROS) have been demonstrated to play an important role as signaling and regulating molecules in human adipocytes. In order to evaluate the differential modulating roles of antioxidants, we treated human adipocytes differentiated from human bone marrow-derived mesenchymal stem cells with MitoQ, resveratrol and curcumin. The effects on ROS, viability, mitochondrial respiration and intracellular ATP levels were examined. MitoQ lowered both oxidizing and reducing ROS. Resveratrol decreased reducing and curcumin oxidizing radicals only. All three substances slightly decreased state III respiration immediately after addition. After 24 h of treatment, MitoQ inhibited both basal and uncoupled oxygen consumption, whereas curcumin and resveratrol had no effect. Intracellular ATP levels were not altered. This demonstrates that MitoQ, resveratrol and curcumin exert potent modulating effects on ROS signaling in human adipocyte with marginal effects on metabolic parameters.

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

NASA Technical Reports Server (NTRS)

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

2000-01-01

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

BCI induces apoptosis via generation of reactive oxygen species and activation of intrinsic mitochondrial pathway in H1299 lung cancer cells.

PubMed

Shin, Jong-Woon; Kwon, Sae-Bom; Bak, Yesol; Lee, Sang-Ku; Yoon, Do-Young

2018-03-28

The compound (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53. Furthermore, BCI treatment increased the level of cellular reactive oxygen species and pre-treatment of cells with N-acetylcysteine markedly attenuated BCI-mediated apoptosis of NCI-H1299 cells. BCI induced cellular morphological changes, inhibited viability, and produced reactive oxygen species in NCI-H1299 cells in a dose-dependent manner. BCI induced processing of caspase-9, caspase-3, and poly ADP-ribose polymerase as well as the release of cytochrome c from the mitochondria into the cytosol. In addition, BCI downregulated Bcl-2 expression and enhanced Bax expression in a dose-dependent manner in NCI-H1299 cells. However, BCI failed to modulate the expression of the death receptor and extrinsic factor caspase-8 and Bid, a linker between the intrinsic and extrinsic apoptotic pathways in NCI-H1299 cells. Thus, BCI induces apoptosis via generation of reactive oxygen species and activation of the intrinsic pathway in NCI-H1299 cells.

Optical studies of oxidative stress in pulmonary artery endothelial cells

NASA Astrophysics Data System (ADS)

Ghanian, Zahra; Sepehr, Reyhaneh; Eis, Annie; Kondouri, Ganesh; Ranji, Mahsa

2015-03-01

Reactive oxygen species (ROS) play an essential role in facilitating signal transduction processes within the cell and modulating the injuries. However, the generation of ROS is tightly controlled both spatially and temporally within the cell, making the study of ROS dynamics particularly difficult. This study present a novel protocol to quantify the dynamic of the mitochondrial superoxide as a precursor of reactive oxygen species. To regulate the mitochondrial superoxide level, metabolic perturbation was induced by administration of potassium cyanide (KCN). The presented method was able to monitor and measure the superoxide production rate over time. Our results demonstrated that the metabolic inhibitor, potassium cyanide (KCN) induced a significant increase in the rate of superoxide production in mitochondria of fetal pulmonary artery endothelial cells (FPAEC). Presented method sets the stage to study different ROS mediated injuries in vitro.

Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion

PubMed Central

Lee, Seung Hyeun; Park, Myung Jae; Choi, Sue In; Lee, Eun Joo; Lee, Sang Yeub; In, Kwang Ho

2017-01-01

Abstract Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P < 0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750–0.886), which was significantly better than that of cytokeratin 19 fragments (P < 0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion. PMID:28121949

Soft Cysteine Signaling Network: The Functional Significance of Cysteine in Protein Function and the Soft Acids/Bases Thiol Chemistry That Facilitates Cysteine Modification.

PubMed

Wible, Ryan S; Sutter, Thomas R

2017-03-20

The unique biophysical and electronic properties of cysteine make this molecule one of the most biologically critical amino acids in the proteome. The defining sulfur atom in cysteine is much larger than the oxygen and nitrogen atoms more commonly found in the other amino acids. As a result of its size, the valence electrons of sulfur are highly polarizable. Unique protein microenvironments favor the polarization of sulfur, thus increasing the overt reactivity of cysteine. Here, we provide a brief overview of the endogenous generation of reactive oxygen and electrophilic species and specific examples of enzymes and transcription factors in which the oxidation or covalent modification of cysteine in those proteins modulates their function. The perspective concludes with a discussion of cysteine chemistry and biophysics, the hard and soft acids and bases model, and the proposal of the Soft Cysteine Signaling Network: a hypothesis proposing the existence of a complex signaling network governed by layered chemical reactivity and cross-talk in which the chemical modification of reactive cysteine in biological networks triggers the reorganization of intracellular biochemistry to mitigate spikes in endogenous or exogenous oxidative or electrophilic stress.

Regulation of singlet oxygen-induced apoptosis by cytosolic NADP+-dependent isocitrate dehydrogenase.

PubMed

Kim, Sun Yee; Lee, Su Min; Tak, Jean Kyoung; Choi, Kyeong Sook; Kwon, Taeg Kyu; Park, Jeen-Woo

2007-08-01

Singlet oxygen is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules and it also promotes deleterious processes such as cell death. Recently, we demonstrated that the control of redox balance and the cellular defense against oxidative damage are the primary functions of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) through supplying NADPH for antioxidant systems. In this report, we demonstrate that modulation of IDPc activity in HL-60 cells regulates singlet oxygen-induced apoptosis. When we examined the protective role of IDPc against singlet oxygen-induced apoptosis with HL-60 cells transfected with the cDNA for mouse IDPc in sense and antisense orientations, a clear inverse relationship was observed between the amount of IDPc expressed in target cells and their susceptibility to apoptosis. The results suggest that IDPc plays an important protective role in apoptosis of HL-60 cells induced by singlet oxygen.

Olive Oil Phenolics Prevent Oxysterol‐Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells, Through Modulation of p38 and JNK Pathways

PubMed Central

Deiana, Monica; Spencer, Jeremy P. E.; Corona, Giulia

2017-01-01

Scope The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells. Methods and results Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin‐1β, regulated on activation, normal T‐cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation. Conclusions These results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes. PMID:28815947

Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation.

PubMed

Previte, Dana M; O'Connor, Erin C; Novak, Elizabeth A; Martins, Christina P; Mollen, Kevin P; Piganelli, Jon D

2017-01-01

The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells. During activation, CD4+ T cells must transition metabolically from oxidative phosphorylation to aerobic glycolysis to support proliferation and effector function. As ROS are capable of modulating cellular metabolism in other models, we sought to understand if blocking ROS also regulates CD4+ T cell activation and effector function by modulating T cell metabolism. To do so, we utilized an ROS scavenging and potent antioxidant manganese metalloporphyrin (MnP). Our results demonstrate that redox modulation during activation regulates the mTOR/AMPK axis by maintaining AMPK activation, resulting in diminished mTOR activation and reduced transition to aerobic glycolysis in diabetogenic splenocytes. These results correlated with decreased Myc and Glut1 upregulation, reduced glucose uptake, and diminished lactate production. In an adoptive transfer model of T1D, animals treated with MnP demonstrated delayed diabetes progression, concurrent with reduced CD4+ T cell activation. Our results demonstrate that ROS are required for driving and sustaining T cell activation-induced metabolic reprogramming, and further support ROS as a target to minimize aberrant immune responses in autoimmunity.

Inverse correlation between reactive oxygen species in unwashed semen and sperm motion parameters as measured by a computer-assisted semen analyzer.

PubMed

Takeshima, Teppei; Yumura, Yasushi; Yasuda, Kengo; Sanjo, Hiroyuki; Kuroda, Shinnosuke; Yamanaka, Hiroyuki; Iwasaki, Akira

2017-01-01

This study investigated the correlation between sperm motion parameters obtained by a computer-assisted semen analyzer and levels of reactive oxygen species in unwashed semen. In total, 847 patients, except for azoospermic patients were investigated. At the time of each patient's first consultation, semen parameters were measured using SMAS™ or CellSoft 3000™, and production of reactive oxygen species was measured using a computer-driven LKB Wallac Luminometer 1251 Analyzer. The patients were divided into two groups: reactive oxygen species - positive and negative. The semen parameters within each group were measured using one of the two computer-assisted semen analyzer systems and then compared. Correlations between reactive oxygen species levels and sperm motion parameters in semen from the reactive oxygen species - positive group were also investigated. Reactive oxygen species were detected in semen samples of 282 cases (33.3%). Sperm concentration (P < 0.01; P < 0.01), motility (P < 0.01; P < 0.05), and progressive motility (P < 0.01; P < 0.01) were markedly lower in the reactive oxygen species - positive group than in the reactive oxygen species - negative group. Among the sperm motion parameters in the reactive oxygen species - positive group, sperm concentration (P < 0.01; P < 0.01), motility (P < 0.05; P < 0.01), mALH (P < 0.05; P < 0.01), and progressive motility (P < 0.05; P < 0.01) also showed inverse correlations with the logarithmic transformed reactive oxygen species levels. Therefore, this study demonstrated that excessive reactive oxygen species in semen damage sperm concentration, motility, and other sperm motion parameters.

Flavonoids: Antioxidants Against Atherosclerosis

PubMed Central

Grassi, Davide; Desideri, Giovambattista; Ferri, Claudio

2010-01-01

Oxidative stress results from an imbalance between excessive formation of reactive oxygen species (ROS) and/or reactive nitrogen species and limited antioxidant defences. Endothelium and nitric oxide (NO) are key regulators of vascular health. NO bioavailability is modulated by ROS that degrade NO, uncouple NO synthase, and inhibit synthesis. Cardiovascular risk conditions contribute to oxidative stress, causing an imbalance between NO and ROS, with a relative decrease in NO bioavailability. Dietary flavonoids represent a range of polyphenolic compounds naturally occurring in plant foods. Flavonoids are potentially involved in cardiovascular prevention mainly by decreasing oxidative stress and increasing NO bioavailability. PMID:22254061

Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes.

PubMed

Meunier, Mathieu; Ancelet, Sarah; Lefebvre, Christine; Arnaud, Josiane; Garrel, Catherine; Pezet, Mylène; Wang, Yan; Faure, Patrice; Szymanski, Gautier; Duployez, Nicolas; Preudhomme, Claude; Biard, Denis; Polack, Benoit; Cahn, Jean-Yves; Moulis, Jean Marc; Park, Sophie

2017-12-01

Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation. We highlight a decreased apoptosis rate and an increased proportion of cycling cells, both leading to higher proliferation rates. The iron chelation properties of low dose DFX failed to activate the Iron Regulatory Proteins and to support iron depletion, but low dose DFX dampers intracellular reactive oxygen species. Furthermore low concentrations of DFX activate the NF-κB pathway in erythroid precursors triggering anti-apoptotic and anti-inflammatory signals. Establishing stable gene silencing of the Thioredoxin (TRX) 1 genes, a NF-κB modulator, showed that fine-tuning of reactive oxygen species (ROS) levels regulates NF-κB. These results justify a clinical trial proposing low dose DFX in MDS patients refractory to erythropoiesis stimulating agents.

Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes

PubMed Central

Meunier, Mathieu; Ancelet, Sarah; Lefebvre, Christine; Arnaud, Josiane; Garrel, Catherine; Pezet, Mylène; Wang, Yan; Faure, Patrice; Szymanski, Gautier; Duployez, Nicolas; Preudhomme, Claude; Biard, Denis; Polack, Benoit; Cahn, Jean-Yves; Moulis, Jean Marc; Park, Sophie

2017-01-01

Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation. We highlight a decreased apoptosis rate and an increased proportion of cycling cells, both leading to higher proliferation rates. The iron chelation properties of low dose DFX failed to activate the Iron Regulatory Proteins and to support iron depletion, but low dose DFX dampers intracellular reactive oxygen species. Furthermore low concentrations of DFX activate the NF-κB pathway in erythroid precursors triggering anti-apoptotic and anti-inflammatory signals. Establishing stable gene silencing of the Thioredoxin (TRX) 1 genes, a NF-κB modulator, showed that fine-tuning of reactive oxygen species (ROS) levels regulates NF-κB. These results justify a clinical trial proposing low dose DFX in MDS patients refractory to erythropoiesis stimulating agents. PMID:29285268

Reactivity-based drug discovery using vitamin B(6)-derived pharmacophores.

PubMed

Wondrak, Georg T

2008-05-01

Endogenous reactive intermediates including photoexcited states of tissue chromophores, reactive oxygen species (ROS), reactive carbonyl species (RCS), transition metal ions, and Schiff bases have been implicated in the initiation and progression of diverse human pathologies including tumorigenesis, atherosclerosis, diabetes, and neurodegenerative disease. In contrast to structure-based approaches that target macromolecules by selective ligands, reactivity-based drug discovery uses chemical reagents as therapeutics that target reactive chemical species involved in human pathology. Reactivity-based design of prototype agents that effectively antagonize, modulate, and potentially even reverse the chemistry underlying tissue damage from oxidative and carbonyl stress therefore holds great promise in delivering significant therapeutic benefit. Apart from its established role as an essential cofactor for numerous enzymes, a large body of evidence suggests that B(6)-vitamers contain reactive pharmacophores that mediate therapeutically useful non-vitamin drug actions as potent antioxidants, metal chelators, carbonyl scavengers, Schiff base forming agents, and photosensitizers. Based on the fascinating chemical versatility of B(6)-derived pharmacophores, B(6)-vitamers are therefore promising lead compounds for reactivity-based drug design.

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

PubMed Central

White, Phillipa C.; Milward, Michael R.; Cooper, Paul R.

2017-01-01

ABSTRACT Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii, stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated. PMID:28947649

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria.

PubMed

Hirschfeld, Josefine; White, Phillipa C; Milward, Michael R; Cooper, Paul R; Chapple, Iain L C

2017-12-01

Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii , stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated. Copyright © 2017 American Society for Microbiology.

Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair

PubMed Central

Freisinger, Chrissy; Rindy, Julie; Golenberg, Netta; Frecentese, Grace; Gibson, Angela; Eliceiri, Kevin W

2018-01-01

Tissue injury leads to early wound-associated reactive oxygen species (ROS) production that mediate tissue regeneration. To identify mechanisms that function downstream of redox signals that modulate regeneration, a vimentin reporter of mesenchymal cells was generated by driving GFP from the vimentin promoter in zebrafish. Early redox signaling mediated vimentin reporter activity at the wound margin. Moreover, both ROS and vimentin were necessary for collagen production and reorganization into projections at the leading edge of the wound. Second harmonic generation time-lapse imaging revealed that the collagen projections were associated with dynamic epithelial extensions at the wound edge during wound repair. Perturbing collagen organization by burn wound disrupted epithelial projections and subsequent wound healing. Taken together our findings suggest that ROS and vimentin integrate early wound signals to orchestrate the formation of collagen-based projections that guide regenerative growth during efficient wound repair. PMID:29336778

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

PubMed Central

Liu, Rui-Ming; Desai, Leena P.

2015-01-01

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

Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion

PubMed Central

Tamura, Masato; Matsui, Hirofumi; Tomita, Tsutomu; Sadakata, Hisato; Indo, Hiroko P.; Majima, Hideyuki J.; Kaneko, Tsuyoshi; Hyodo, Ichinosuke

2014-01-01

Tumor invasion is the most important factor to decide patient’s prognosis. The relation between reactive oxygen species and tumor invasion is mainly reported that nicotinamide adenine dinucleotide phosphate oxidase in the cell membrane is a reactive oxygen species producer for formulating an invadopodia. On the other hand, mitochondrion was known as one of the most important reactive oxygen species-producer in the cell via an energy transfer system. However, the relation between mitochondrial reactive oxygen species and the tumor invasion was not well clarified. In this study, we evaluated the relation between mitochondrial reactive oxygen species and tumor invasion using a normal gastric mucosal cell-line (RGM-1) and a cancerous mutant RGM-1 cell-line (RGK-1). Manganese superoxide dismutase-expressing RGK-1 cell-lines were used for a scavenging mitochondrial reactive oxygen species. The cells have been evaluated their movement ability as follows; cellular ruffling frequencies, wound healing assay to evaluate horizontal cellular migration, and invasion assay using matrigel to analyze vertical cellular migration. All cellular movement abilities were inhibited by scavenging mitochondrial reactive oxygen species with manganese superoxide dismutase. Therefore mitochondrial reactive oxygen species was one of factors enhancing the tumor invasion in gastric cancer. PMID:24426185

Myeloid-derived suppressor cells modulate B-cell responses.

PubMed

Lelis, Felipe J N; Jaufmann, Jennifer; Singh, Anurag; Fromm, Katja; Teschner, Annkathrin Chiara; Pöschel, Simone; Schäfer, Iris; Beer-Hammer, Sandra; Rieber, Nikolaus; Hartl, Dominik

2017-08-01

Myeloid-derived suppressor cells (MDSCs) are key regulators of adaptive immunity by suppressing T-cell functions. However, their potential action on or interaction with B cells remained poorly understood. Here we demonstrate that human polymorphonuclear MDSCs differentially modulate B-cell function by suppressing B-cell proliferation and antibody production. We further demonstrate that this MDSC-mediated effect is cell contact dependent and involves established mediators such as arginase-1, nitric oxide (NO), reactive oxygen species (ROS) as well as B-cell death. Collectively, our studies provide novel evidence that human MDSCs modulate B cells, which could have future implications for immunotherapy approaches. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells.

PubMed

Li, Yuan; Zou, Xuan; Gao, Jing; Cao, Ke; Feng, Zhihui; Liu, Jiankang

2018-05-24

Impairment of retinal pigment epithelial (RPE) cells is considered a key contributor to the development of age-related macular degeneration. Apoptosis-related protein 3 (APR3) was recently discovered after treatment with all- trans retinoic acid, a pivotal molecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity. Overexpression of APR3 revealed its mitochondrial localization and induced a robust production of reactive oxygen species that was accompanied by impaired mitochondrial oxygen consumption, complex activity, and lower ATP content, resulting in significant changes in mitochondrial structure, which may contribute to cell apoptosis. High doses of all- trans retinoic acid treatment were found to significantly induce APR3 expression, increase reactive oxygen species levels, and decrease ATP content, which were abolished by knockdown of APR3. These results indicate that APR3 plays a vital role in regulating redox status and mitochondrial activity and thus suggest APR3 might be a potential novel target for study of treatment of age-related macular degeneration.-Li, Y., Zou, X., Gao, J., Cao, K., Feng, Z., Liu, J. APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells.

Role of Ambient Gas Composition on Cold Physical Plasma-Elicited Cell Signaling in Keratinocytes.

PubMed

Schmidt, Anke; Bekeschus, Sander; Jablonowski, Helena; Barton, Annemarie; Weltmann, Klaus-Dieter; Wende, Kristian

2017-06-06

A particularly promising medical application of cold physical plasma is the support of wound healing. This is presumably achieved by modulating inflammation as well as skin cell signaling and migration. Plasma-derived reactive oxygen and nitrogen species (ROS/RNS) are assumed the central biologically active plasma components. We hypothesized that modulating the environmental plasma conditions from pure nitrogen (N 2 ) to pure oxygen (O 2 ) in an atmospheric pressure argon plasma jet (kINPen) will change type and concentration of ROS/RNS and effectively tune the behavior of human skin cells. To investigate this, HaCaT keratinocytes were studied in vitro with regard to cell metabolism, viability, growth, gene expression signature, and cytokine secretion. Flow cytometry demonstrated only slight effects on cytotoxicity. O 2 shielding provided stronger apoptotic effects trough caspase-3 activation compared to N 2 shielding. Gene array technology revealed induction of signaling and communication proteins such as immunomodulatory interleukin 6 as well as antioxidative and proproliferative molecules (HMOX1, VEGFA, HBEGF, CSF2, and MAPK) in response to different plasma shielding gas compositions. Cell response was correlated to reactive species: oxygen-shielding plasma induces a cell response more efficiently despite an apparent decrease of hydrogen peroxide (H 2 O 2 ), which was previously shown to be a major player in plasma-cell regulation, emphasizing the role of non-H 2 O 2 ROS like singlet oxygen. Our results suggest differential effects of ROS- and RNS-rich plasma, and may have a role in optimizing clinical plasma applications in chronic wounds. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

In vitro characterization of cutaneous immunotoxicity of immortalized human keratinocytes (HaCaT) exposed to reactive and disperse textile dyes.

PubMed

Leme, Daniela Morais; Sehr, Andrea; Grummt, Tamara; Gonçalves, Jenifer Pendiuk; Jacomasso, Thiago; Winnischofer, Sheila Maria Brochado; Potrich, Francine Bittencourt; Oliveira, Carolina Camargo de; Trindade, Edvaldo da Silva; de Oliveira, Danielle Palma

2018-05-01

Several synthetic dyes are used by textile industry for supplying the market of colored clothes. However, these chemicals have been associated with a variety of adverse human health effects, including textile dermatitis. Thus, there is a growing concern to identify textile dyes potentially as skin immunotoxicants. The aim of this in vitro study was to characterize the immunotoxic potential of reactive (Reactive Green 19 [RG19], Reactive Blue 2 [RB2], Reactive Black 5 [RB5]) and disperse (Disperse Red 1 [DR1]) textile dyes using a dermal cell line. For this purpose, a cell-based approach was conducted with immortalized human keratinocytes (KC) (HaCaT) using selected biomarkers of cutaneous inflammation including modulation of matrix metalloproteinases (MMP), oxidative stress such as reactive oxygen species (ROS) generation, and inflammatory cytokine profile. DR1 was the only dye able to trigger an immune response such as release of IL-12 cytokine, a potent co-stimulator of T helper 1 cell, which may be considered as a skin immunotoxicant. The reactive dyes including RB5 that were previously reported as skin sensitizers failed to induce inflammatory reactions under the conditions tested. The reactive dyes studied may pose a risk to human KC by induction of effects related to modulation of MMP-2 (RB5) and -9 (RB5 and RB2) and generation of ROS (RG19 and RB2). Thus, all these dyes need to be used with caution to avoid undesirable effects to consumers who may be exposed dermally.

Variation in reactive oxygen species concentration among lettuce types and modulation of their production via PPO during E. coli O157:H7 colonization of injured lettuce leaves(Abstract)

USDA-ARS?s Scientific Manuscript database

Minimally processed leafy vegetables are the biggest culprits in produce-linked outbreaks of foodborne illness and E. coli O157:H7 (EcO157) is the predominant causal agent of these epidemics. Harvesting and processing cause plant lesions thus creating new niches for opportunistic colonization of lea...

Vibrio parahaemolyticus strengthens their virulence through modulation of cellular reactive oxygen species in vitro

PubMed Central

El-Malah, Shimaa S.; Yang, Zhenquan; Hu, Maozhi; Li, Qiuchun; Pan, Zhiming; Jiao, Xinan

2014-01-01

Vibrio parahaemolyticus (Vp) is one of the emergent food-borne pathogens that are commensally associated with various shellfish species throughout the world. It is strictly environmental and many strains are pathogenic to humans. The virulent strains cause distinct diseases, including wound infections, septicemia, and most commonly, acute gastroenteritis, which is acquired through the consumption of raw or undercooked seafood, especially shellfish. Vp has two type three secretion systems (T3SSs), which triggering its cytotoxicity and enterotoxicity via their effectors. To better understand the pathogenesis of Vp, we established a cell infection model in vitro using a non-phagocytic cell line. Caco-2 cells were infected with different strains of Vp (pandemic and non-pandemic strains) and several parameters of cytotoxicity were measured together with adhesion and invasion indices, which reflect the pathogen's virulence. Our results show that Vp adheres to cell monolayers and can invade non-phagocytic cells. It also survives and persists in non-phagocytic cells by modulating reactive oxygen species (ROS), allowing its replication, and resulting in complete cellular destruction. We conclude that the pathogenicity of Vp is based on its capacities for adhesion and invasion. Surprisingly's; enhanced of ROS resistance period could promote the survival of Vp inside the intestinal tract, facilitating tissue infection by repressing the host's oxidative stress response. PMID:25566508

Cell Proliferation, Reactive Oxygen and Cellular Glutathione

PubMed Central

Day, Regina M.; Suzuki, Yuichiro J.

2005-01-01

A variety of cellular activities, including metabolism, growth, and death, are regulated and modulated by the redox status of the environment. A biphasic effect has been demonstrated on cellular proliferation with reactive oxygen species (ROS)—especially hydrogen peroxide and superoxide—in which low levels (usually submicromolar concentrations) induce growth but higher concentrations (usually >10–30 micromolar) induce apoptosis or necrosis. This phenomenon has been demonstrated for primary, immortalized and transformed cell types. However, the mechanism of the proliferative response to low levels of ROS is not well understood. Much of the work examining the signal transduction by ROS, including H2O2, has been performed using doses in the lethal range. Although use of higher ROS doses have allowed the identification of important signal transduction pathways, these pathways may be activated by cells only in association with ROS-induced apoptosis and necrosis, and may not utilize the same pathways activated by lower doses of ROS associated with increased cell growth. Recent data has shown that low levels of exogenous H2O2 up-regulate intracellular glutathione and activate the DNA binding activity toward antioxidant response element. The modulation of the cellular redox environment, through the regulation of cellular glutathione levels, may be a part of the hormetic effect shown by ROS on cell growth. PMID:18648617

The Role of Reactive-Oxygen-Species in Microbial Persistence and Inflammation

PubMed Central

Spooner, Ralee; Yilmaz, Özlem

2011-01-01

The mechanisms of chronic infections caused by opportunistic pathogens are of keen interest to both researchers and health professionals globally. Typically, chronic infectious disease can be characterized by an elevation in immune response, a process that can often lead to further destruction. Reactive-Oxygen-Species (ROS) have been strongly implicated in the aforementioned detrimental response by host that results in self-damage. Unlike excessive ROS production resulting in robust cellular death typically induced by acute infection or inflammation, lower levels of ROS produced by host cells are increasingly recognized to play a critical physiological role for regulating a variety of homeostatic cellular functions including growth, apoptosis, immune response, and microbial colonization. Sources of cellular ROS stimulation can include “danger-signal-molecules” such as extracellular ATP (eATP) released by stressed, infected, or dying cells. Particularly, eATP-P2X7 receptor mediated ROS production has been lately found to be a key modulator for controlling chronic infection and inflammation. There is growing evidence that persistent microbes can alter host cell ROS production and modulate eATP-induced ROS for maintaining long-term carriage. Though these processes have yet to be fully understood, exploring potential positive traits of these “injurious” molecules could illuminate how opportunistic pathogens maintain persistence through physiological regulation of ROS signaling. PMID:21339989

Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species Production in Nickel Hyperaccumulator Alyssum murale*

PubMed Central

Agrawal, Bhavana; Czymmek, Kirk J.; Sparks, Donald L.; Bais, Harsh P.

2013-01-01

Mitochondria are important targets of metal toxicity and are also vital for maintaining metal homeostasis. Here, we examined the potential role of mitochondria in homeostasis of nickel in the roots of nickel hyperaccumulator plant Alyssum murale. We evaluated the biochemical basis of nickel tolerance by comparing the role of mitochondria in closely related nickel hyperaccumulator A. murale and non-accumulator Alyssum montanum. Evidence is presented for the rapid and transient influx of nickel in root mitochondria of nickel hyperaccumulator A. murale. In an early response to nickel treatment, substantial nickel influx was observed in mitochondria prior to sequestration in vacuoles in the roots of hyperaccumulator A. murale compared with non-accumulator A. montanum. In addition, the mitochondrial Krebs cycle was modulated to increase synthesis of malic acid and citric acid involvement in nickel hyperaccumulation. Furthermore, malic acid, which is reported to form a complex with nickel in hyperaccumulators, was also found to reduce the reactive oxygen species generation induced by nickel. We propose that the interaction of nickel with mitochondria is imperative in the early steps of nickel uptake in nickel hyperaccumulator plants. Initial uptake of nickel in roots results in biochemical responses in the root mitochondria indicating its vital role in homeostasis of nickel ions in hyperaccumulation. PMID:23322782

Transient Influx of nickel in root mitochondria modulates organic acid and reactive oxygen species production in nickel hyperaccumulator Alyssum murale.

PubMed

Agrawal, Bhavana; Czymmek, Kirk J; Sparks, Donald L; Bais, Harsh P

2013-03-08

Mitochondria are important targets of metal toxicity and are also vital for maintaining metal homeostasis. Here, we examined the potential role of mitochondria in homeostasis of nickel in the roots of nickel hyperaccumulator plant Alyssum murale. We evaluated the biochemical basis of nickel tolerance by comparing the role of mitochondria in closely related nickel hyperaccumulator A. murale and non-accumulator Alyssum montanum. Evidence is presented for the rapid and transient influx of nickel in root mitochondria of nickel hyperaccumulator A. murale. In an early response to nickel treatment, substantial nickel influx was observed in mitochondria prior to sequestration in vacuoles in the roots of hyperaccumulator A. murale compared with non-accumulator A. montanum. In addition, the mitochondrial Krebs cycle was modulated to increase synthesis of malic acid and citric acid involvement in nickel hyperaccumulation. Furthermore, malic acid, which is reported to form a complex with nickel in hyperaccumulators, was also found to reduce the reactive oxygen species generation induced by nickel. We propose that the interaction of nickel with mitochondria is imperative in the early steps of nickel uptake in nickel hyperaccumulator plants. Initial uptake of nickel in roots results in biochemical responses in the root mitochondria indicating its vital role in homeostasis of nickel ions in hyperaccumulation.

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

PubMed Central

Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

2013-01-01

Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

Observation of oscillatory surface reactions of riboflavin, trolox, and singlet oxygen using single carbon nanotube fluorescence spectroscopy.

PubMed

Sen, Fatih; Boghossian, Ardemis A; Sen, Selda; Ulissi, Zachary W; Zhang, Jingqing; Strano, Michael S

2012-12-21

Single-molecule fluorescent microscopy allows semiconducting single-walled carbon nanotubes (SWCNTs) to detect the adsorption and desorption of single adsorbate molecules as a stochastic modulation of emission intensity. In this study, we identify and assign the signature of the complex decomposition and reaction pathways of riboflavin in the presence of the free radical scavenger Trolox using DNA-wrapped SWCNT sensors dispersed onto an aminopropyltriethoxysilane (APTES) coated surface. SWCNT emission is quenched by riboflavin-induced reactive oxygen species (ROS), but increases upon the adsorption of Trolox, which functions as a reductive brightening agent. Riboflavin has two parallel reaction pathways, a Trolox oxidizer and a photosensitizer for singlet oxygen and superoxide generation. The resulting reaction network can be detected in real time in the vicinity of a single SWCNT and can be completely described using elementary reactions and kinetic rate constants measured independently. The reaction mechanism results in an oscillatory fluorescence response from each SWCNT, allowing for the simultaneous detection of multiple reactants. A series-parallel kinetic model is shown to describe the critical points of these oscillations, with partition coefficients on the order of 10(-6)-10(-4) for the reactive oxygen and excited state species. These results highlight the potential for SWCNTs to characterize complex reaction networks at the nanometer scale.

House dust mite-induced asthma causes oxidative damage and DNA double-strand breaks in the lungs.

PubMed

Chan, Tze Khee; Loh, Xin Yi; Peh, Hong Yong; Tan, W N Felicia; Tan, W S Daniel; Li, Na; Tay, Ian J J; Wong, W S Fred; Engelward, Bevin P

2016-07-01

Asthma is related to airway inflammation and oxidative stress. High levels of reactive oxygen and nitrogen species can induce cytotoxic DNA damage. Nevertheless, little is known about the possible role of allergen-induced DNA damage and DNA repair as modulators of asthma-associated pathology. We sought to study DNA damage and DNA damage responses induced by house dust mite (HDM) in vivo and in vitro. We measured DNA double-strand breaks (DSBs), DNA repair proteins, and apoptosis in an HDM-induced allergic asthma model and in lung samples from asthmatic patients. To study DNA repair, we treated mice with the DSB repair inhibitor NU7441. To study the direct DNA-damaging effect of HDM on human bronchial epithelial cells, we exposed BEAS-2B cells to HDM and measured DNA damage and reactive oxygen species levels. HDM challenge increased lung levels of oxidative damage to proteins (3-nitrotyrosine), lipids (8-isoprostane), and nucleic acid (8-oxoguanine). Immunohistochemical evidence for HDM-induced DNA DSBs was revealed by increased levels of the DSB marker γ Histone 2AX (H2AX) foci in bronchial epithelium. BEAS-2B cells exposed to HDM showed enhanced DNA damage, as measured by using the comet assay and γH2AX staining. In lung tissue from human patients with asthma, we observed increased levels of DNA repair proteins and apoptosis, as shown by caspase-3 cleavage, caspase-activated DNase levels, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. Notably, NU7441 augmented DNA damage and cytokine production in the bronchial epithelium and apoptosis in the allergic airway, implicating DSBs as an underlying driver of asthma pathophysiology. This work calls attention to reactive oxygen and nitrogen species and HDM-induced cytotoxicity and to a potential role for DNA repair as a modulator of asthma-associated pathophysiology. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[Pulse-modulated Electromagnetic Radiation of Extremely High Frequencies Protects Cellular DNA against Damaging Effect of Physico-Chemical Factors in vitro].

PubMed

Gapeyev, A B; Lukyanova, N A

2015-01-01

Using a comet assay technique, we investigated protective effects of. extremely high frequency electromagnetic radiation in combination with the damaging effect of X-ray irradiation, the effect of damaging agents hydrogen peroxide and methyl methanesulfonate on DNA in mouse whole blood leukocytes. It was shown that the preliminary exposure of the cells to low intensity pulse-modulated electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20-min exposure, modulation frequencies of 1 and 16 Hz) caused protective effects decreasing the DNA damage by 20-45%. The efficacy of pulse-modulated electromagnetic radiation depended on the type of genotoxic agent and increased in a row methyl methanesulfonate--X-rays--hydrogen peroxide. Continuous electromagnetic radiation was ineffective. The mechanisms of protective effects may be connected with an induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated electromagnetic radiation.

Modulation of Invading and Resident Inflammatory Cell Activation as a Novel Way to Mitigate Spinal Cord Injury-Associated Neuropathic Pain

DTIC Science & Technology

2017-09-01

alcohol consumption alone and in combination with SCI on the same inflammatory and neuropathic endpoints, as well as the ameliorative effects of CBD...inflammatory outcomes: 100% complete CY16 Goals Quantify markers following alcohol consumption : 100% complete Investigate combined alcohol/SCI...events such as generation of reactive oxygen and nitrogen species, chemokine and cytokine release, microglial and astrocytic activation, and T cell

Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells.

PubMed

Sawa, Kenta; Uematsu, Takumi; Korenaga, Yusuke; Hirasawa, Ryuya; Kikuchi, Masatoshi; Murata, Kyohei; Zhang, Jian; Gai, Xiaoqing; Sakamoto, Kazuichi; Koyama, Tomoyuki; Satoh, Takumi

2017-03-16

Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity. These three intermediates reduced the production of hydrogen peroxide-activated reactive oxygen species, measured in terms of 2',7'-dichlorofluorescein diacetate fluorescence. In contrast, none of the KCIs-used at 1 mM-protected against cell death induced by high concentrations of glutamate-another type of oxidative stress-induced neuronal cell death. Because these protective KCIs did not have any toxic effects (at least up to 10 mM), they have potential use for therapeutic intervention against chronic neurodegenerative diseases.

The toxic Doppelganger: on the ionic and molecular mimicry of cadmium.

PubMed

Chmielowska-Bąk, Jagna; Izbiańska, Karolina; Deckert, Joanna

2013-01-01

Cadmium is a toxic heavy metal which can cause numerous alterations in cell functioning. Exposure to cadmium leads to generation of reactive oxygen species, disorders in membrane structure and functioning, inhibition of respiration, disturbances in ion homeostasis, perturbations in cell division, and initiation of apoptosis and necrosis. This heavy metal is considered a carcinogen by the Agency for Toxic Substances and Disease Registry. At least some of the described toxic effects could result from the ability of cadmium to mimic other divalent ions and alert signal transduction networks. This review describes the role of cadmium mimicry in its uptake, reactive oxygen species generation, alterations in calmodulin, Wnt/β-catenin and estrogen signaling pathways, and modulation of neurotransmission. The last section is dedicated to the single known case of a favorable function performed by cadmium mimicry: marine diatoms, which live in zinc deficient conditions, utilize cadmium as a cofactor in carbonic anhydrase - so far the only described cadmium enzyme.

Continuous process for singlet oxygenation of hydrophobic substrates in microemulsion using a pervaporation membrane.

PubMed

Caron, Laurent; Nardello, Véronique; Mugge, José; Hoving, Erik; Alsters, Paul L; Aubry, Jean-Marie

2005-02-15

Chemically generated singlet oxygen (1O2, 1Deltag) is able to oxidize a great deal of hydrophobic substrates from molybdate-catalyzed hydrogen peroxide decomposition, provided a suitable reaction medium such as a microemulsion system is used. However, high substrate concentrations or poorly reactive organics require large amounts of H2O2 that generate high amounts of water and thus destabilize the system. We report results obtained on combining dark singlet oxygenation of hydrophobic substrates in microemulsions with a pervaporation membrane process. To avoid composition alterations after addition of H2O2 during the peroxidation, the reaction mixture circulates through a ceramic membrane module that enables a partial and selective dewatering of the microemulsion. Optimization phase diagrams of sodium molybdate/water/alcohol/anionic surfactant/organic solvent have been elaborated to maximize the catalyst concentration and therefore the reaction rate. The membrane selectivity towards the mixture constituents has been investigated showing that a high retention is observed for the catalyst, for organic solvents and hydrophobic substrates, but not for n-propanol (cosurfactant) and water. The efficiency of such a process is illustrated with the peroxidation of a poorly reactive substrate, viz., beta-pinene.

Apoptotic effects of bovine apo-lactoferrin on HeLa tumor cells.

PubMed

Luzi, Carla; Brisdelli, Fabrizia; Iorio, Roberto; Bozzi, Argante; Carnicelli, Veronica; Di Giulio, Antonio; Lizzi, Anna Rita

2017-01-01

Lactoferrin (Lf), a cationic iron-binding glycoprotein of 80 kDa present in body secretions, is known as a compound with marked antimicrobial activity. In the present study, the apoptotic effect of iron-free bovine lactoferrin (apo-bLf) on human epithelial cancer (HeLa) cells was examined in association with reactive oxygen species and glutathione (GSH) levels. Apoptotic effect of iron-free bovine lactoferrin inhibited the growth of HeLa cells after 48 hours of treatment while the diferric-bLf was ineffective in the concentration range tested (from 1 to 12.5 μM). Western blot analysis showed that key apoptotic regulators including Bax, Bcl-2, Sirt1, Mcl-1, and PARP-1 were modulated by 1.25 μM of apo-bLf. In the same cell line, apo-bLf induced apoptosis together with poly (ADP-ribose) polymerase cleavage, caspase activation, and a significant drop of NAD + . In addition, apo-bLf-treated HeLa cells showed a marked increase of reactive oxygen species level and a significant GSH depletion. On the whole, apo-bLf triggered apoptosis of HeLa cells upon oxygen radicals burst and GSH decrease. Copyright © 2017 John Wiley & Sons, Ltd.

Hypoxia promotes Mycobacterium tuberculosis-specific up-regulation of granulysin in human T cells.

PubMed

Zenk, Sebastian F; Vollmer, Michael; Schercher, Esra; Kallert, Stephanie; Kubis, Jan; Stenger, Steffen

2016-06-01

Oxygen tension affects local immune responses in inflammation and infection. In tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. Oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular Mycobacterium tuberculosis (M.Tb). The effect of oxygen restriction on T cell-mediated antimicrobial effector mechanisms is unknown. Therefore we determined the influence of hypoxia on the expression of granulysin, an antimicrobial peptide of lymphocytes. Hypoxia increased the antigen-specific up-regulation of granulysin mRNA and protein in human CD4(+) and CD8(+) T lymphocytes. This observation was functionally relevant, because oxygen restriction supported the growth-limiting effect of antigen-specific T cells against virulent M.Tb residing in primary human macrophages. Our results provide evidence that oxygen restriction promotes the expression of granulysin and suggest that this effect-in conjunction with additional T cell-mediated immune responses-supports protection against mycobacteria. The therapeutic modulation of oxygen availability may offer a new strategy for the host-directed therapy of infectious diseases with intracellular pathogens.

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

PubMed Central

McBean, Gethin; Cindric, Marina; Egea, Javier; López, Manuela G.; Rada, Patricia; Zarkovic, Neven

2014-01-01

Abstract Neurodegenerative diseases are characterized by chronic microglial over-activation and oxidative stress. It is now beginning to be recognized that reactive oxygen species (ROS) produced by either microglia or the surrounding environment not only impact neurons but also modulate microglial activity. In this review, we first analyze the hallmarks of pro-inflammatory and anti-inflammatory phenotypes of microglia and their regulation by ROS. Then, we consider the production of reactive oxygen and nitrogen species by NADPH oxidases and nitric oxide synthases and the new findings that also indicate an essential role of glutathione (γ-glutamyl-l-cysteinylglycine) in redox homeostasis of microglia. The effect of oxidant modification of macromolecules on signaling is analyzed at the level of oxidized lipid by-products and sulfhydryl modification of microglial proteins. Redox signaling has a profound impact on two transcription factors that modulate microglial fate, nuclear factor kappa-light-chain-enhancer of activated B cells, and nuclear factor (erythroid-derived 2)-like 2, master regulators of the pro-inflammatory and antioxidant responses of microglia, respectively. The relevance of these proteins in the modulation of microglial activity and the interplay between them will be evaluated. Finally, the relevance of ROS in altering blood brain barrier permeability is discussed. Recent examples of the importance of these findings in the onset or progression of neurodegenerative diseases are also discussed. This review should provide a profound insight into the role of redox homeostasis in microglial activity and help in the identification of new promising targets to control neuroinflammation through redox control of the brain. Antioxid. Redox Signal. 21, 1766–1801. PMID:24597893

Nitric Oxide Is Associated with Long-Term Zinc Tolerance in Solanum nigrum1[W

PubMed Central

Xu, Jin; Yin, Hengxia; Li, Yulong; Liu, Xiaojing

2010-01-01

Nitric oxide (NO) has been identified as a signal molecule that interplays with reactive oxygen species in response to heavy metal stresses. Roles of NO in regulating cadmium toxicity and iron deficiency have been proposed; however, the function of NO in zinc (Zn) tolerance in plants remains unclear. Here, we investigated NO accumulation and its role in plant Zn tolerance. Zn-induced NO production promoted an increase in reactive oxygen species accumulation in Solanum nigrum roots by modulating the expression and activity of antioxidative enzymes. Subsequently, programmed cell death (PCD) was observed in primary root tips. Inhibiting NO accumulation by 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (a specific NO scavenger) or NG-nitro-l-arginine-methyl ester (a NO synthase inhibitor) prevented the increase of superoxide radical and hydrogen peroxide as well as the subsequent cell death in the root tips, supporting the role of NO in Zn-induced PCD in the root tips. Zn-induced NO production affected the length of primary roots, the number of lateral roots, and root hair growth and thereby modulated root system architecture and activity. Investigation of metal contents in Zn-treated roots suggests that NO is required for metal (especially iron) uptake and homeostasis in plants exposed to excess Zn. Taken together, our results indicate that NO production and the subsequent PCD in root tips exposed to excess Zn are favorable for the S. nigrum seedling response to long-term Zn toxicity by modulating root system architecture and subsequent adaptation to Zn stress. PMID:20855519

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

PubMed

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

2015-03-01

A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Prolonged exposure of resveratrol induces reactive superoxide species-independent apoptosis in murine prostate cells.

PubMed

Kumar, Sanjay; Stokes, James; Singh, Udai P; Scissum-Gunn, Karyn; Singh, Rajesh; Manne, Upender; Mishra, Manoj K

2017-10-01

Nitric oxide, a signaling molecule, inhibits mitochondrial respiration by binding with cytochrome c oxidase, resulting in elevated production of reactive superoxide species (reactive oxygen and nitrogen) in the mitochondria and increased susceptibility to cell death. Generation of mitochondrial superoxide species can be suppressed by natural compounds such as resveratrol, a dietary polyphenol found in the skin of red fruits. In various cancer cells, resveratrol shows anti-oxidant and cancer preventive properties. Since, the effect of resveratrol on reactive superoxide species-independent apoptosis in prostate cancer cells is not well illustrated; therefore, we investigated this phenomenon in TRAMP murine prostate cancer cells. To accomplish this, TRAMP cells were incubated with resveratrol, resveratrol + DETA-NONOate, DETA-NONOate (nitric oxide donor), resveratrol + L-NMMA, or L-NMMA (nitric oxide inhibitor) for 48 h, and reactive superoxide species in the mitochondria and culture supernatant were measured. In addition, the mitochondrial membrane potential, cell viability, expression of apoptotic markers (Bax and Bcl2), γ-H2A.x, p53, and caspase-3 was determined. We found that resveratrol suppressed reactive superoxide species such as reactive oxygen species in the mitochondria and nitric oxide in culture supernatant when compared to the DETA-NONOate treatment and disrupted the mitochondrial membrane potential. Resveratrol also reduced cell viability, altered the expression of apoptotic markers (Bax and Bcl2), and increased expression of γ-H2A.x (indicative marker of DNA fragmentation) and p53 (a critical DNA damage response protein). However, there was no appreciable modulation of the caspase-3. Therefore, our data suggest that resveratrol induces superoxide species-independent apoptosis and may act as a therapeutic agent against prostate cancer.

Feed gas contaminant removal in ion transport membrane systems

DOEpatents

Underwood, Richard Paul [Allentown, PA; Makitka, III, Alexander; Carolan, Michael Francis [Allentown, PA

2012-04-03

An oxygen ion transport membrane process wherein a heated oxygen-containing gas having one or more contaminants is contacted with a reactive solid material to remove the one or more contaminants. The reactive solid material is provided as a deposit on a support. The one or more contaminant compounds in the heated oxygen-containing gas react with the reactive solid material. The contaminant-depleted oxygen-containing gas is contacted with a membrane, and oxygen is transported through the membrane to provide transported oxygen.

Gut Microbiota: A Key Modulator of Intestinal Healing in Inflammatory Bowel Disease.

PubMed

Lopetuso, L R; Petito, V; Zambrano, D; Orlando, D; Dal Lago, A; Serrichhio, L; Papa, A; Gasbarrini, A; Scaldaferri, F

2016-01-01

Mucosal healing (MH) represents a crucial factor for maintaining gut homeostasis. Indeed, in inflammatory bowel disease, MH has become the standard therapeutical target, because it is associated with more effective disease control, more frequent steroid-free remission, lower rates of hospitalization and surgery, and improved quality of life. In this scenario, gut microbiota is a crucial player in modulating intestinal repair and regeneration process. It can act on the tumor necrosis factor-α production, modulation of reactive oxygen and nitrogen species, activity of matrix metalloproteinases and on many other mechanisms strictly involved in restoring gut health. In this review, we analyze and review the literature on the role of gut microbiota in sustaining mucosal injury and achieving MH. © 2016 S. Karger AG, Basel.

Metabolism as a Target for Modulation in Autoimmune Diseases.

PubMed

Huang, Nick; Perl, Andras

2018-05-05

Metabolic pathways are now well recognized as important regulators of immune differentiation and activation, and thus influence the development of autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanistic target of rapamycin (mTOR) has emerged as a key sensor of metabolic stress and an important mediator of proinflammatory lineage specification. Metabolic pathways control the production of mitochondrial reactive oxygen species (ROS), which promote mTOR activation and also modulate the antigenicity of proteins, lipids, and DNA, thus placing ROS at the heart of metabolic disturbances during pathogenesis of SLE. Therefore, we review here the pathways that control ROS production and mTOR activation and identify targets for safe therapeutic modulation of the signaling network that underlies autoimmune diseases, focusing on SLE. Copyright © 2018. Published by Elsevier Ltd.

Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways.

PubMed

Dayem, Ahmed Abdal; Kim, BongWoo; Gurunathan, Sangiliyandi; Choi, Hye Yeon; Yang, Gwangmo; Saha, Subbroto Kumar; Han, Dawoon; Han, Jihae; Kim, Kyeongseok; Kim, Jin-Hoi; Cho, Ssang-Goo

2014-07-01

Nano-scale materials are noted for unique properties, distinct from those of their bulk material equivalents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Human neuroblastoma SH-SY5Y cells are considered an ideal in vitro model for studying neurogenesis, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and downregulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs modulate the intracellular signaling pathways, leading to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxidative Stress Induces Disruption of the Axon Initial Segment

PubMed Central

Clark, Kareem C.; Sword, Brooke A.; Dupree, Jeffrey L.

2017-01-01

The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex. PMID:29228786

Regulation of NADPH-dependent Nitric Oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive NADPH analogue

PubMed Central

Rouaud, Florian; Romero-Perez, Miguel; Wang, Huan; Lobysheva, Irina; Ramassamy, Booma; Henry, Etienne; Tauc, Patrick; Giacchero, Damien; Boucher, Jean-Luc; Deprez, Eric; Rocchi, Stéphane; Slama-Schwok, Anny

2014-01-01

Nitric Oxide (NO) and Reactive oxygen species (ROS) are endogenous regulators of angiogenesis-related events as endothelial cell proliferation and survival, but NO/ROS defect or unbalance contribute to cancers. We recently designed a novel photoactive inhibitor of NO-Synthases (NOS) called NS1, which binds their NADPH site in vitro. Here, we show that NS1 inhibited NO formed in aortic rings. NS1-induced NO decrease led to an inhibition of angiogenesis in a model of VEGF-induced endothelial tubes formation. Beside this effect, NS1 reduced ROS levels in endothelial and melanoma A375 cells and in aorta. In metastatic melanoma cells, NS1 first induced a strong decrease of VEGF and blocked melanoma cell cycle at G2/M. NS1 decreased NOX4 and ROS levels that could lead to a specific proliferation arrest and cell death. In contrast, NS1 did not perturb melanocytes growth. Altogether, NS1 revealed a possible cross-talk between eNOS- and NOX4 –associated pathways in melanoma cells via VEGF, Erk and Akt modulation by NS1 that could be targeted to stop proliferation. NS1 thus constitutes a promising tool that modulates NO and redox stresses by targeting and directly inhibiting eNOS and, at least indirectly, NADPH oxidase(s), with great potential to control angiogenesis. PMID:25296975

[Modulating Effect of Extracellular HSP70 on Generation of Reactive Oxigen Species in Populations of Phagocytes].

PubMed

Troyanova, N I; Shevchenko, M A; Boyko, A A; Mirzoyev, R R; Pertseva, M A; Kovalenko, E I; Sapozhnikov, A M

2015-01-01

Reactive oxygen species (ROS) produced by phagocytic cells of the innate immune system play an important role in the first line of defense protecting the host from pathogens. The NADPH oxidase multi-subunit complex is the main source of ROS in all types of the phagocytes. Formation of the membrane-associated enzyme complex and its activity are dependent on many different factors controlling both intensification and suppression of the ROS production rate. However, the evidences are emerging in recent years indicating existence of poorly studied mechanisms of restriction of ROS generation level in phagocytes directed at protection of host tissues in the sites of inflammation from destruction caused by the oxygen free radicals. Our previous data and results of other authors demonstrate that a mechanism of the limitation of ROS production by phagocytes may by connected with immunomodulating activity of extracellular pool. of HSP70. In the present work, we used inhibitors of NADPH oxidase and in vitro cultures of different phagocytes to study a possible relationship between down-regulating effect of exogenous HSP70 on ROS generation and the interaction of the protein with the enzyme subunits. Our results confirmed the literature data concerning the ability of extracellular HSP70 to modulate NADPH oxidase activity and demonstrated for the first time an inhibitory effect of the protein on intracellular ROS generation in phagocytes.

Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling

PubMed Central

Zhao, Zhongfu; Koltai, Erika; Ohno, Hideki; Atalay, Mustafa

2013-01-01

Abstract The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein–protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling. Antioxid. Redox Signal. 18, 1208–1246. PMID:22978553

Biochemistry of free radicals: from electrons to tissues.

PubMed

Boveris, A

1998-01-01

Free radicals are chemical species with an unpaired electron in the outer valence orbitals. The unpaired electron makes them paramagnetic (physics) and relatively reactive (chemistry). The free radicals that are normal metabolites in aerobic biological systems have varied reactivities, ranging from the high reactivity of hydroxyl radical (t1/2 = 10(-9) s) to the low reactivity of melanins (t1/2 = days). The univalent reduction of oxygen that takes place in mammalian organs produces superoxide radicals at a rate of about 2% of the total oxygen uptake. The primary production of superoxide radicals sustains a free radical chain reaction involving a series of reactive oxygen species (hydrogen peroxide, hydroxyl and peroxyl radical and singlet oxygen). Nitric oxide is almost unreactive as free radical except for its termination reaction with superoxide radical to yield the strong oxidant peroxynitrite. Nitric oxide also reacts with ubiquinol in a redox reaction, with cytochrome oxidase competitively with oxygen, and oxymyoglobin and oxyhemoglobin displacing oxygen. Septic shock and endotoxemia produce muscle dysfunction and oxidative stress due to increased steady state concentrations of reactive oxygen and nitrogen species.

Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Beck, Michael W.; Derrick, Jeffrey S.; Kerr, Richard A.; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C.; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D.; Kim, Kwang S.; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

2016-10-01

The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease.

PubMed

Beck, Michael W; Derrick, Jeffrey S; Kerr, Richard A; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D; Kim, Kwang S; Lee, Joo-Yong; Ruotolo, Brandon T; Lim, Mi Hee

2016-10-13

The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy.

PubMed

To, Eunice E; Vlahos, Ross; Luong, Raymond; Halls, Michelle L; Reading, Patrick C; King, Paul T; Chan, Christopher; Drummond, Grant R; Sobey, Christopher G; Broughton, Brad R S; Starkey, Malcolm R; van der Sluis, Renee; Lewin, Sharon R; Bozinovski, Steven; O'Neill, Luke A J; Quach, Tim; Porter, Christopher J H; Brooks, Doug A; O'Leary, John J; Selemidis, Stavros

2017-07-12

The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irrespective of the infecting strain. Reactive oxygen species are ancient processes that protect plants, fungi and animals against invading pathogens including bacteria. However, in mammals reactive oxygen species production paradoxically promotes virus pathogenicity by mechanisms not yet defined. Here we identify that the primary enzymatic source of reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide generation, which suppresses antiviral and humoral signaling networks via modification of a unique, highly conserved cysteine residue (Cys98) on Toll-like receptor-7. Accordingly, targeted inhibition of endosomal reactive oxygen species production abrogates influenza A virus pathogenicity. We conclude that endosomal reactive oxygen species promote fundamental molecular mechanisms of viral pathogenicity, and the specific targeting of this pathogenic process with endosomal-targeted reactive oxygen species inhibitors has implications for the treatment of viral disease.Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.

Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

PubMed

Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

2006-07-01

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis

PubMed Central

Huang, Long Shuang; Mathew, Biji; Zhao, Yutong; Noth, Imre; Reddy, Sekhar P.; Harijith, Anantha; Usatyuk, Peter V.; Berdyshev, Evgeny V.; Kaminski, Naftali; Zhou, Tong; Zhang, Wei; Zhang, Yanmin; Rehman, Jalees; Kotha, Sainath R.; Gurney, Travis O.; Parinandi, Narasimham L.; Lussier, Yves A.; Garcia, Joe G. N.

2014-01-01

Rationale: Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis. Objectives: To define a role for LYCAT in human and murine models of pulmonary fibrosis. Methods: We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge. Measurements and Main Results: LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. LYCAT mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, hLYCAT overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. In vitro studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection. Conclusions: This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis. PMID:24779708

Pancreatic two P domain K+ channels TALK-1 and TALK-2 are activated by nitric oxide and reactive oxygen species

PubMed Central

Duprat, F; Girard, C; Jarretou, G; Lazdunski, M

2005-01-01

This study firstly shows with in situ hybridization on human pancreas that TALK-1 and TALK-2, two members of the 2P domain potassium channel (K2P) family, are highly and specifically expressed in the exocrine pancreas and absent in Langherans islets. On the contrary, expression of TASK-2 in mouse pancreas is found both in the exocrine pancreas and in the Langherans islets. This study also shows that TALK-1 and TALK-2 channels, expressed in Xenopus oocytes, are strongly and specifically activated by nitric oxide (obtained with a mixture of sodium nitroprussate (SNP) and dithiothreitol (DTT)), superoxide anion (obtained with xanthine and xanthine oxidase) and singlet oxygen (obtained upon photoactivation of rose bengal, and with chloramine T). Other nitric oxide and reactive oxygen species (NOS and ROS) donors, as well as reducing conditions were found to be ineffective on TALK-1, TALK-2 and TASK-2 (sin-1, angeli's salt, SNP alone, tBHP, H2O2, and DTT). These results suggest that, in the exocrine pancreas, specific members of the NOS and ROS families could act as endogenous modulators of TALK channels with a role in normal secretion as well as in disease states such as acute pancreatitis and apoptosis. PMID:15513946

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

PubMed Central

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

2017-01-01

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

Pharmaceutical and nutraceutical effects of Pinus pinaster bark extract

PubMed Central

Iravani, S.; Zolfaghari, B.

2011-01-01

In everyday life, our body generates free radicals and other reactive oxygen species which are derived either from the endogenous metabolic processes (within the body) or from external sources. Many clinical and pharmacological studies suggest that natural antioxidants can prevent oxidative damage. Among the natural antioxidant products, Pycnogenol® (French Pinus pinaster bark extract) has been received considerable attention because of its strong free radical-scavenging activity against reactive oxygen and nitrogen species. P. pinaster bark extract (PBE) contains polyphenolic compounds (these compounds consist of catechin, taxifolin, procyanidins of various chain lengths formed by catechin and epicatechin units, and phenolic acids) capable of producing diverse potentially protective effects against chronic and degenerative diseases. This herbal medication has been reported to have cardiovascular benefits, such as vasorelaxant activity, angiotensin-converting enzyme inhibiting activity, and the ability to enhance the microcirculation by increasing capillary permeability. Moreover, effects on the immune system and modulation of nitrogen monoxide metabolism have been reported. This article provides a brief overview of clinical studies describing the beneficial and health-promoting effects of PBE. PMID:22049273

Tangeretin reduces ultraviolet B (UVB)-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking mitogen-activated protein kinase (MAPK) activation and reactive oxygen species (ROS) generation.

PubMed

Yoon, Ji Hye; Lim, Tae-Gyu; Lee, Kyung Mi; Jeon, Ae Ji; Kim, Su Yeon; Lee, Ki Won

2011-01-12

The present study examined the effects of tangeretin, a polymethoxylated flavonone present in citrus fruits, on ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression in JB6 P+ mouse skin epidermal cells. Tangeretin suppressed UVB-induced COX-2 expression and transactivation of nuclear factor-κB and activator protein-1 in JB6 P+ cells. Moreover, tangeretin blocked UVB-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38, and attenuated the phosphorylation of MAPK kinases 1/2, 3/6, and 4. Tangeretin also limited the endogenous generation of reactive oxygen species (ROS), thereby protecting the cells against oxidative stress. However, tangeretin did not scavenge the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and influence the nicotinamide adenine dinucleotide phosphate oxidase activity. These results suggest that the anti-inflammatory effects of tangeretin stem from its modulation of cell signaling and suppression of intracellular ROS generation. Tangeretin may have a potent chemopreventive effect in skin cancer.

Ion channels in inflammation.

PubMed

Eisenhut, Michael; Wallace, Helen

2011-04-01

Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles.

PubMed

Lavado, Andrea S; Chauhan, Veeren M; Zen, Amer Alhaj; Giuntini, Francesca; Jones, D Rhodri E; Boyle, Ross W; Beeby, Andrew; Chan, Weng C; Aylott, Jonathan W

2015-09-14

Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(II) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(II) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(II) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.

Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

PubMed Central

Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

2015-01-01

Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

Caloric restriction improves efficiency and capacity of the mitochondrial electron transport chain in Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Joon-Seok; Choi, Kyung-Mi; Lee, Cheol-Koo, E-mail: cklee2005@korea.ac.kr

2011-06-03

Highlights: {yields} Calorie restriction (CR) increases electron transport chain (ETC) at both RNA and protein level. {yields} CR enhances mitochondrial membrane potential, and, regardless of ages, reduces reactive oxygen species. {yields} CR increases both efficiency and capacity of the ETC. {yields} CR induces intensive modulation at mitochondrial ETC where might be a major site leading to extension of lifespan. -- Abstract: Caloric restriction (CR) is known to extend lifespan in a variety of species; however, the mechanism remains unclear. In this study, we found that CR potentiated the mitochondrial electron transport chain (ETC) at both the transcriptional and translational levels.more » Indeed, mitochondrial membrane potential (MMP) was increased by CR, and, regardless of ages, overall reactive oxygen species (ROS) generation was decreased by CR. With these changes, overall growth rate of cells was maintained under various CR conditions, just like cells under a non-restricted condition. All of these data support increased efficiency and capacity of the ETC by CR, and this change might lead to extension of lifespan.« less

Induction of apoptosis by N-(4-hydroxyphenyl)retinamide and its association with reactive oxygen species, nuclear retinoic acid receptors, and apoptosis-related genes in human prostate carcinoma cells.

PubMed

Sun, S Y; Yue, P; Lotan, R

1999-03-01

The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been shown to induce apoptosis in various malignant cells including human prostate carcinoma cells (HPC). We examined several possible mechanisms by which 4HPR could induce apoptosis in HPC cells. 4HPR exhibited concentration- and time-dependent decrease in cell number both in androgen-dependent (LNCaP) and -independent (DU145 and PC-3) cells. The 4HPR concentrations causing 50% decrease in cell number in LNCaP, DU145, and PC-3 cultures were 0.9 +/- 0.16, 4.4 +/- 0.45, and 3.0 +/- 1.0 microM, respectively, indicating that LNCaP cells were more sensitive to 4HPR than the other cells. 4HPR-induced apoptosis in all three cell lines was evidenced by increased enzymatic labeling of DNA breaks and formation of a DNA ladder. 4HPR increased the level of reactive oxygen species, especially in LNCaP cells. 4HPR-induced apoptosis could be suppressed in LNCaP cells by antioxidant and in DU145 cells by a nuclear retinoic acid receptor-specific antagonist, suggesting the involvement of reactive oxygen species or retinoic acid receptors in mediating apoptosis induced by 4HPR in the different HPC cells. Furthermore, 4HPR modulated the expression levels of some apoptosis-related gene (p21, c-myc, and c-jun), which may also contribute to the induction of apoptosis by 4HPR in HPC cells.

6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms.

PubMed

Wu, Jung-Ju; Omar, Hany A; Lee, Ying-Ray; Teng, Yen-Ni; Chen, Pin-Shern; Chen, Yu-Chung; Huang, Hsiao-Shan; Lee, Kuan-Han; Hung, Jui-Hsiang

2015-09-05

Shogaols are a group of the active constituents of ginger that have been identified to have various biological activities. The aim of the current study was to investigate the antitumor activity of 6-shogaol in hepatocellular carcinoma (HCC) and the possible involvement of reactive oxygen species as a putative mechanism of action. HCC cell lines, HepG2 and Huh-7, were used to study the in vitro anti-cancer activity of 6-shogaol via the application of various molecular biology techniques. Results showed that 6-shogaol effectively inhibited the cell viability, caused cell cycle arrest at G2/M phase and induced apoptosis in HCC cells as indicated by MTT assay, DAPI nuclear staining, annexin V assay, cell cycle analysis, and activation of caspase-3. Western blot analysis revealed the ability of 6-shogaol to target cancer survival signaling pathways mediated by mitogen-activated protein kinase (MAPK), 5' AMP-activated protein kinase (AMPK) and Akt. In addition, 6-Shogaol induced alteration of cyclin proteins expression and caused cleavage of protein kinase C delta. Furthermore, 6-Shogaol was able to induce the production of reactive oxygen species and endoplasmic reticulum (ER) stress-associated proteins and the consequent activation of autophagy in HepG2 cells. Taken together, the current study highlights evidences that 6-shogaol induces apoptosis, modulates cyclins expression and targets cancer survival signaling pathways in HCC cell lines, at least in part, via the production of reactive oxygen species. These findings support 6-shogaol's clinical promise as a potential candidate for HCC therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed Central

Sestili, Piero

2015-01-01

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

Reactive Oxygen Species in Cardiovascular Disease

PubMed Central

Sugamura, Koichi; Keaney, John F.

2011-01-01

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

Mitochondrial reactive oxygen species modulate innate immune response to influenza A virus in human nasal epithelium.

PubMed

Kim, Sujin; Kim, Min-Ji; Park, Do Yang; Chung, Hyo Jin; Kim, Chang-Hoon; Yoon, Joo-Heon; Kim, Hyun Jik

2015-07-01

The innate immune system of the nasal epithelium serves as a first line of defense against invading respiratory viruses including influenza A virus (IAV). Recently, it was verified that interferon (IFN)-related immune responses play a critical role in local antiviral innate immunity. Reactive oxygen species (ROS) generation by exogenous pathogens has also been demonstrated in respiratory epithelial cells and modulation of ROS has been reported to be important for respiratory virus-induced innate immune mechanisms. Passage-2 normal human nasal epithelial (NHNE) cells were inoculated with IAV (WS/33, H1N1) to assess the sources of IAV-induced ROS and the relationship between ROS and IFN-related innate immune responses. Both STAT1 and STAT2 phosphorylation and the mRNA levels of IFN-stimulated genes, including Mx1, 2,5-OAS1, IFIT1, and CXCL10, were induced after IAV infection up to three days post infection. Similarly, we observed that mitochondrial ROS generation increased maximally at 2 days after IAV infection. After suppression of mitochondrial ROS generation, IAV-induced phosphorylation of STAT and mRNA levels of IFN-stimulated genes were attenuated and actually, viral titers of IAV were significantly higher in cases with scavenging ROS. Our findings suggest that mitochondrial ROS might be responsible for controlling IAV infection and may be potential sources of ROS generation, which is required to initiate an innate immune response in NHNE cells. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

Chandrasekara, Anoma; Shahidi, Fereidoon

2011-01-12

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

Activatable albumin-photosensitizer nanoassemblies for triple-modal imaging and thermal-modulated photodynamic therapy of cancer.

PubMed

Hu, Dehong; Sheng, Zonghai; Gao, Guanhui; Siu, Fungming; Liu, Chengbo; Wan, Qian; Gong, Ping; Zheng, Hairong; Ma, Yifan; Cai, Lintao

2016-07-01

Photodynamic therapy (PDT) is a noninvasive and effective approach for cancer treatment. The main bottlenecks of clinical PDT are poor selectivity of photosensitizer and inadequate oxygen supply resulting in serious side effects and low therapeutic efficiency. Herein, a thermal-modulated reactive oxygen species (ROS) strategy using activatable human serum albumin-chlorin e6 nanoassemblies (HSA-Ce6 NAs) for promoting PDT against cancer is developed. Through intermolecular disulfide bond crosslinking and hydrophobic interaction, Ce6 photosensitizer is effectively loaded into the HSA NAs, and the obtained HSA-Ce6 NAs exhibit excellent reduction response, as well as enhanced tumor accumulation and retention. By the precision control of the overall body temperature instead of local tumor temperature increasing from 37 °C to 43 °C, the photosensitization reaction rate of HSA-Ce6 NAs increases 20%, and the oxygen saturation of tumor tissue raise 52%, significantly enhancing the generation of ROS for promoting PDT. Meanwhile, the intrinsic fluorescence and photoacoustic properties, and the chelating characteristic of porphyrin ring can endow the HSA-Ce6 NAs with fluorescence, photoacoustic and magnetic resonance triple-modal imaging functions. Upon irradiation of low-energy near-infrared laser, the tumors are completely suppressed without tumor recurrence and therapy-induced side effects. The robust thermal-modulated ROS strategy combined with albumin-based activatable nanophotosensitizer is highly potential for multi-modal imaging-guided PDT and clinical translation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vacuum ultraviolet radiation/atomic oxygen synergism in materials reactivity

NASA Technical Reports Server (NTRS)

Koontz, Steven; Leger, Lubert; Albyn, Keith; Cross, Jon

1990-01-01

Experimental results are presented which indicate that low fluxes of vacuum UV (VUV) radiation exert a pronounced influence on the atomic oxygen reactivity of such fluorocarbon and fluorocarbon spacecraft materials as the FEP Teflon and PCTFE that are under consideration for the Space Station Freedom. With simultaneous exposure to VUV fluxes comparable to those experienced in LEO, the reactivity of these materials becomes comparable to that of Kapton; VUV radiation has also been shown to increase the reactivity of Kapton with thermal-energy oxygen atoms.

Characterizing Myeloid Cell Activation in NF1 Vasculopathy

DTIC Science & Technology

2017-07-01

stimulation of its receptor (CCR2) and the generation of reactive oxygen species, which are generated in excessive quantities by neurofibromin-deficient...macrophages via monocyte chemotactic peptide-1 (MCP-1) stimulation of its receptor (CCR2) and the generation of reactive oxygen species, which are...neurofibromatosis; stenosis; aneurysm; MCP-1; CCR2; reactive oxygen species; superoxide; macrophages; monocytes; arteries; cardiovascular disease Major

Microcarbon-based facial creams activate aerial oxygen under light to reactive oxygen species damaging cell

NASA Astrophysics Data System (ADS)

Maity, Sheli; Pakhira, Bholanath; Ghosh, Subrata; Saha, Royina; Sarkar, Ripon; Barui, Ananya; Sarkar, Sabyasachi

2017-11-01

Nanosized reduced graphene oxide (rGO) is found in active microcarbon used in popular face cream from the manufacturers like Ponds, Nevia, and Garnier which, under visible light exposure, gets activated by aerial oxygen to generate reactive oxygen species (ROS) harmful to skin.

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

PubMed

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. © 2016 American Heart Association, Inc.

Effects of peptides on generation of reactive oxygen species in subcellular fractions of Drosophila melanogaster.

PubMed

Khavinson, V K; Myl'nikov, S V; Oparina, T I; Arutyunyan, A V

2001-07-01

We studied the effects of Epithalon (Ala-Glu-Asp-Gly) and Vilon (Lys-Glu) on free radical processes in highly inbred HA(+)line of Drosophila melanogaster. Vilon inhibited generation of reactive oxygen species in mitochondria, but stimulated this process in the cytosol. We found sex- and age-related differences in the generation of reactive oxygen species and cytosol antioxidant activity.

Plateau Waves of Intracranial Pressure and Partial Pressure of Cerebral Oxygen.

PubMed

Lang, Erhard W; Kasprowicz, Magdalena; Smielewski, Peter; Pickard, John; Czosnyka, Marek

2016-01-01

This study investigates 55 intracranial pressure (ICP) plateau waves recorded in 20 patients after severe traumatic brain injury (TBI) with a focus on a moving correlation coefficient between mean arterial pressure (ABP) and ICP, called PRx, which serves as a marker of cerebrovascular reactivity, and a moving correlation coefficient between ABP and cerebral partial pressure of oxygen (pbtO2), called ORx, which serves as a marker for cerebral oxygen reactivity. ICP and ICPamplitude increased significantly during the plateau waves, whereas CPP and pbtO2 decreased significantly. ABP, ABP amplitude, and heart rate remained unchanged. In 73 % of plateau waves PRx increased during the wave. ORx showed an increase during and a decrease after the plateau waves, which was not statistically significant. Our data show profound cerebral vasoparalysis on top of the wave and, to a lesser extent, impairment of cerebral oxygen reactivity. The different behavior of the indices may be due to the different latencies of the cerebral blood flow and oxygen level control mechanisms. While cerebrovascular reactivity is a rapidly reacting mechanism, cerebral oxygen reactivity is slower.

Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

PubMed Central

Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

2013-01-01

It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

Production and Consumption of Reactive Oxygen Species by Fullerenes

EPA Science Inventory

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

Oxygen and Oxygen Toxicity: The Birth of Concepts

PubMed Central

Zhu, Hong; Traore, Kassim; Santo, Arben; Trush, Michael A.; Li, Y. Robert

2018-01-01

Molecular dioxygen (O2) is an essential element of aerobic life, yet incomplete reduction or excitation of O2 during aerobic metabolisms generates diverse oxygen-containing reactive species, commonly known as reactive oxygen species (ROS). On the one hand, ROS pose a serious threat to aerobic organisms via inducing oxidative damage to cellular constituents. On the other hand, these reactive species, when their generation is under homeostatic control, also play important physiological roles (e.g., constituting an important component of immunity and participating in redox signaling). This article defines oxygen and the key facts about oxygen, and discusses the relationship between oxygen and the emergence of early animals on Earth. The article then describes the discovery of oxygen by three historical figures and examines the birth of the concepts of oxygen toxicity and the underlying free radical mechanisms. The article ends with a brief introduction to the emerging field of ROS-mediated redox signaling and physiological responses. PMID:29707642

Bio-Physicochemical Interactions of Engineered Nanomaterials in in Vitro Cell Culture Model

DTIC Science & Technology

2014-10-11

are the important factors to study their toxicity . To investigate the potential role of oxidative stress as a mechanism of toxicity , reactive oxygen...of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO) lactate dehydrogenase (LDH) level and reduction in...potential role of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH) level

A mitochondria-targeted turn-on fluorescent probe for the detection of glutathione in living cells.

PubMed

Zhang, Jian; Bao, Xiaolong; Zhou, Junliang; Peng, Fangfang; Ren, Hang; Dong, Xiaochun; Zhao, Weili

2016-11-15

A novel turn-on red fluorescent BODIPY-based probe (Probe 1) for the detection of glutathione was developed. Such a probe carries a para-dinitrophenoxy benzyl pyridinium moiety at the meso position of a BODIPY dye as self-immolative linker. Probe 1 responds selectively to glutathione with the detection limit of 109nM over other amino acids, common metal ions, reactive oxygen species, reactive nitrogen species, and reactive sulfur species. A novel electrostatic interaction to modulate the SNAr attack of glutathione was believed to play significant role for the observed selective response to glutathione. The cleavage of dinitrophenyl ether by glutathione leads to the production of para-hydroxybenzyl moiety which is able to self-immolate through an intramolecular 1,4-elimination reaction to release the fluorescent BODIPY dye. The low toxic probe has been successfully used to detect mitochondrial glutathione in living cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Equatorial Ligand Perturbations Influence the Reactivity of Manganese(IV)-Oxo Complexes.

PubMed

Massie, Allyssa A; Denler, Melissa C; Cardoso, Luísa Thiara; Walker, Ashlie N; Hossain, M Kamal; Day, Victor W; Nordlander, Ebbe; Jackson, Timothy A

2017-04-03

Manganese(IV)-oxo complexes are often invoked as intermediates in Mn-catalyzed C-H bond activation reactions. While many synthetic Mn IV -oxo species are mild oxidants, other members of this class can attack strong C-H bonds. The basis for these reactivity differences is not well understood. Here we describe a series of Mn IV -oxo complexes with N5 pentadentate ligands that modulate the equatorial ligand field of the Mn IV center, as assessed by electronic absorption, electron paramagnetic resonance, and Mn K-edge X-ray absorption methods. Kinetic experiments show dramatic rate variations in hydrogen-atom and oxygen-atom transfer reactions, with faster rates corresponding to weaker equatorial ligand fields. For these Mn IV -oxo complexes, the rate enhancements are correlated with both 1) the energy of a low-lying 4 E excited state, which has been postulated to be involved in a two-state reactivity model, and 2) the Mn III/IV reduction potentials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

PubMed Central

Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

2014-01-01

Objective To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-α mRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 µg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-α mRNA expression in the cells at concentrations of 50 µg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions. PMID:25182441

Influence of reactive oxygen species on the sterilization of microbes

USDA-ARS?s Scientific Manuscript database

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

Using Paraquat to Generate Anion Free Radicals and Hydrogen Peroxide in "In Vitro": Antioxidant Effect of Vitamin E--A Procedure to Teach Theoretical and Experimental Principles of Reactive Oxygen Species Biochemistry

ERIC Educational Resources Information Center

Jimenez-Del-Rio, Marlene; Suarez-Cedeno, Gerson; Velez-Pardo, Carlos

2010-01-01

The theoretical basis of reactive oxygen species and their impact on health issues are relatively easy to understand by biomedical students. The detection of reactive oxygen species requires expensive equipment, the procedures are time consuming and costly, and the results are hard to interpret. Moreover, cause-and-effect relationships in the…

Modulation of monocytic leukemia cell function and survival by high gradient magnetic fields and mathematical modeling studies.

PubMed

Zablotskii, Vitalii; Syrovets, Tatiana; Schmidt, Zoe W; Dejneka, Alexandr; Simmet, Thomas

2014-03-01

The influence of spatially modulated high gradient magnetic fields on cellular functions of human THP-1 leukemia cells is studied. We demonstrate that arrays of high-gradient micrometer-sized magnets induce i) cell swelling, ii) prolonged increased ROS production, and iii) inhibit cell proliferation, and iv) elicit apoptosis of THP-1 monocytic leukemia cells in the absence of chemical or biological agents. Mathematical modeling indicates that mechanical stress exerted on the cells by high magnetic gradient forces is responsible for triggering cell swelling and formation of reactive oxygen species followed by apoptosis. We discuss physical aspects of controlling cell functions by focused magnetic gradient forces, i.e. by a noninvasive and nondestructive physical approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Host-Toxoplasma gondii Coadaptation Leads to Fine Tuning of the Immune Response.

PubMed

Brasil, Thaís Rigueti; Freire-de-Lima, Celio Geraldo; Morrot, Alexandre; Vetö Arnholdt, Andrea Cristina

2017-01-01

Toxoplasma gondii has successfully developed strategies to evade host's immune response and reach immune privileged sites, which remains in a controlled environment inside quiescent tissue cysts. In this review, we will approach several known mechanisms used by the parasite to modulate mainly the murine immune system at its favor. In what follows, we review recent findings revealing interference of host's cell autonomous immunity and cell signaling, gene expression, apoptosis, and production of microbicide molecules such as nitric oxide and oxygen reactive species during parasite infection. Modulation of host's metalloproteinases of extracellular matrix is also discussed. These immune evasion strategies are determinant to parasite dissemination throughout the host taking advantage of cells from the immune system to reach brain and retina, crossing crucial hosts' barriers.

Host-Toxoplasma gondii Coadaptation Leads to Fine Tuning of the Immune Response

PubMed Central

Brasil, Thaís Rigueti; Freire-de-Lima, Celio Geraldo; Morrot, Alexandre; Vetö Arnholdt, Andrea Cristina

2017-01-01

Toxoplasma gondii has successfully developed strategies to evade host’s immune response and reach immune privileged sites, which remains in a controlled environment inside quiescent tissue cysts. In this review, we will approach several known mechanisms used by the parasite to modulate mainly the murine immune system at its favor. In what follows, we review recent findings revealing interference of host’s cell autonomous immunity and cell signaling, gene expression, apoptosis, and production of microbicide molecules such as nitric oxide and oxygen reactive species during parasite infection. Modulation of host’s metalloproteinases of extracellular matrix is also discussed. These immune evasion strategies are determinant to parasite dissemination throughout the host taking advantage of cells from the immune system to reach brain and retina, crossing crucial hosts’ barriers. PMID:28955329

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

PubMed

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

2017-02-28

Extensive research over the past half a century indicates that reactive oxygen species (ROS) play an important role in cancer. Although low levels of ROS can be beneficial, excessive accumulation can promote cancer. One characteristic of cancer cells that distinguishes them from normal cells is their ability to produce increased numbers of ROS and their increased dependence on an antioxidant defense system. ROS are produced as a byproduct intracellularly by mitochondria and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs, xenobiotics, and radiation. ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to cellular transformation, inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic changes in genes, which is helpful in diagnosing diseases. This review considers the role of ROS in the various stages of cancer development. Finally, we provide evidence that nutraceuticals derived from Mother Nature are highly effective in eliminating cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chlorogenic acid ameliorates alcohol-induced liver injuries through scavenging reactive oxygen species.

PubMed

Kim, Hyunjin; Pan, Jeong Hoon; Kim, Sung Hwan; Lee, Jin Hyup; Park, Jeen-Woo

2018-05-19

The key role of oxidative stress in alcoholic liver disease (ALD) has been established by the large body of evidence from previous studies. Excessive consumption of ethanol induces the production of a variety of reactive oxygen species (ROS) in the liver, such as superoxide, H 2 O 2 , and hydroxyl radical. These products activate oxidant-sensitive signaling cascades and modulators of apoptosis. Because ROS accumulation is closely related to ALD, a number of studies have investigated the benefits of antioxidants. Recent studies demonstrated that polyphenol chlorogenic acid (CGA) has antioxidant properties and health benefits, such as reduction of relative risk of cardiovascular diseases and hepatoprotective effects against acetaminophen toxicity. However, the protective effects of CGA against ALD have not been studied in detail. We hypothesize that CGA plays a role in preventing ALD through its antioxidant properties. In this study, we investigated the protective effects of CGA against liver injuries in vivo. Reduced alcohol-induced-steatosis, apoptotic cell death, and fibrosis due to reduced levels of oxidative stress were observed. These findings suggest that CGA treatment can be an effective approach to attenuate ALD through the suppression of oxidative stress. Copyright © 2018. Published by Elsevier B.V.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

PubMed Central

Jenrow, Kenneth A.; Brown, Stephen L.

2014-01-01

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs. PMID:25324981

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Na; Su, Dian; Cort, John R.

Reversible disulfide oxidation between proximal cysteines in proteins represents a common regulatory control mechanism to modulate flux through metabolic pathways in response to changing environmental conditions. To enable in vivo measurements of cellular redox changes linked to disulfide bond formation, we have synthesized a cell-permeable monosubstituted cyanine dye derivatized with arsenic (i.e., TRAP_Cy3) to trap and visualize dithiols in cytosolic proteins. Alkylation of reactive thiols prior to displacement of the bound TRAP-Cy3 by ethanedithiol permits facile protein capture and mass spectrometric identification of proximal reduced dithiols to the exclusion of individual cysteines. Applying TRAP_Cy3 to evaluate cellular responses to increasesmore » in oxygen and light levels in the photosynthetic microbe Synechococcus sp. PCC 7002, we observe large decreases in the abundance of reduced dithiols in cellular proteins, which suggest redox-dependent mechanisms involving the oxidation of proximal disulfides. Under these same growth conditions that result in the oxidation of proximal thiols, there is a reduction in the abundance of post-translational oxidative modifications involving nitrotyrosine and methionine sulfoxide formation. These results suggest that the redox status of proximal cysteines respond to environmental conditions, acting to regulate metabolic flux and minimize the formation of reactive oxygen species to decrease oxidative protein damage.« less

Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by modulating cyclic-di-GMP levels.

PubMed

Chua, Song Lin; Ding, Yichen; Liu, Yang; Cai, Zhao; Zhou, Jianuan; Swarup, Sanjay; Drautz-Moses, Daniela I; Schuster, Stephan Christoph; Kjelleberg, Staffan; Givskov, Michael; Yang, Liang

2016-11-01

The host immune system offers a hostile environment with antimicrobials and reactive oxygen species (ROS) that are detrimental to bacterial pathogens, forcing them to adapt and evolve for survival. However, the contribution of oxidative stress to pathogen evolution remains elusive. Using an experimental evolution strategy, we show that exposure of the opportunistic pathogen Pseudomonas aeruginosa to sub-lethal hydrogen peroxide (H 2 O 2 ) levels over 120 generations led to the emergence of pro-biofilm rough small colony variants (RSCVs), which could be abrogated by l-glutathione antioxidants. Comparative genomic analysis of the RSCVs revealed that mutations in the wspF gene, which encodes for a repressor of WspR diguanylate cyclase (DGC), were responsible for increased intracellular cyclic-di-GMP content and production of Psl exopolysaccharide. Psl provides the first line of defence against ROS and macrophages, ensuring the survival fitness of RSCVs over wild-type P. aeruginosa Our study demonstrated that ROS is an essential driving force for the selection of pro-biofilm forming pathogenic variants. Understanding the fundamental mechanism of these genotypic and phenotypic adaptations will improve treatment strategies for combating chronic infections. © 2016 The Authors.

Plant Survival in a Changing Environment: The Role of Nitric Oxide in Plant Responses to Abiotic Stress

PubMed Central

Simontacchi, Marcela; Galatro, Andrea; Ramos-Artuso, Facundo; Santa-María, Guillermo E.

2015-01-01

Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant’s ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant’s priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signaling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation. PMID:26617619

Anticancer Vitamin K3 Analogs: A Review.

PubMed

Badave, Kirti D; Khan, Ayesha A; Rane, Sandhya Y

2016-01-01

Menadione (Vitamin K3) comprises of 1,4-naphthoquinone (NQ) moiety that can form redox isomers such as napthosemiquinone (NSQ) and catechol by accepting one or two electrons, respectively. The quinone redox cycling ability leads to the generation of "reactive oxygen species" (ROS) as well as arylation reactions, which are of biological relevance. This ability can be modulated with the help of suitable derivatization. A pharmacophore can be appended at suitable position of Vitamin K3 to have a synergistic or additive effect. In the present review, an attempt has been made to accrue such derivatives modified at 1 or 2 position and evaluated for their cytotoxicity activity on different series of human cancer cell lines such as HeLa, HL-60 and MCF- 7 etc. Production of reactive oxygen species (ROS) and mitochondrial dysfunction caused by Vitamin K3 derivatives leads to apoptosis and tumor inhibition. Recently, the CR-108 compound has shown to exhibit oxidative path together with non-oxidative phosphorylation of p38 MAP kinase in human breast cancer cells. Thus the chemical-biological interactions have been discussed which can be further extrapolated for the development of a potent anticancer drug. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Redox-Modulated Phenomena and Radiation Therapy: The Central Role of Superoxide Dismutases

PubMed Central

Holley, Aaron K.; Miao, Lu; St. Clair, Daret K.

2014-01-01

Abstract Significance: Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged directly by radiation or indirectly through reactive oxygen species (ROS) formed from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting from altered aerobic metabolism. Recent Advances: ROS are produced as a byproduct of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers. ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs modulate the radioresponsiveness of tissues, thus affecting the efficacy of radiotherapy. Critical Issues: Despite its prevalent use, radiation therapy suffers from certain limitations that diminish its effectiveness, including tumor hypoxia and normal tissue damage. Oxygen is important for the stabilization of radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness of radiation therapy against tumor tissues while minimizing normal tissue injury. Future Directions: Because of the importance of ROS in the response of normal and cancer tissues to ionizing radiation, methods that differentially modulate the ROS scavenging ability of cells may prove to be an important method to increase the radiation response in cancer tissues and simultaneously mitigate the damaging effects of ionizing radiation on normal tissues. Altering the expression or activity of SODs may prove valuable in maximizing the overall effectiveness of ionizing radiation. Antioxid. Redox Signal. 20, 1567–1589. PMID:24094070

Ursodeoxycholic acid inhibits overexpression of P-glycoprotein induced by doxorubicin in HepG2 cells.

PubMed

Komori, Yuki; Arisawa, Sakiko; Takai, Miho; Yokoyama, Kunihiro; Honda, Minako; Hayashi, Kazuhiko; Ishigami, Masatoshi; Katano, Yoshiaki; Goto, Hidemi; Ueyama, Jun; Ishikawa, Tetsuya; Wakusawa, Shinya

2014-02-05

The hepatoprotective action of ursodeoxycholic acid (UDCA) was previously suggested to be partially dependent on its antioxidative effect. Doxorubicin (DOX) and reactive oxygen species have also been implicated in the overexpression of P-glycoprotein (P-gp), which is encoded by the MDR1 gene and causes antitumor multidrug resistance. In the present study, we assessed the effects of UDCA on the expression of MDR1 mRNA, P-gp, and intracellular reactive oxygen species levels in DOX-treated HepG2 cells and compared them to those of other bile acids. DOX-induced increases in reactive oxygen species levels and the expression of MDR1 mRNA were inhibited by N-acetylcysteine, an antioxidant, and the DOX-induced increase in reactive oxygen species levels and DOX-induced overexpression of MDR1 mRNA and P-gp were inhibited by UDCA. Cells treated with UDCA showed improved rhodamine 123 uptake, which was decreased in cells treated with DOX alone. Moreover, cells exposed to DOX for 24h combined with UDCA accumulated more DOX than that of cells treated with DOX alone. Thus, UDCA may have inhibited the overexpression of P-gp by suppressing DOX-induced reactive oxygen species production. Chenodeoxycholic acid (CDCA) also exhibited these effects, whereas deoxycholic acid and litocholic acid were ineffective. In conclusion, UDCA and CDCA had an inhibitory effect on the induction of P-gp expression and reactive oxygen species by DOX in HepG2 cells. The administration of UDCA may be beneficial due to its ability to prevent the overexpression of reactive oxygen species and acquisition of multidrug resistance in hepatocellular carcinoma cells. Copyright © 2013 Elsevier B.V. All rights reserved.

Manipulation of arginase expression modulates abiotic stress tolerance in Arabidopsis: effect on arginine metabolism and ROS accumulation

PubMed Central

Chan, Zhulong

2013-01-01

Arginine is an important medium for the transport and storage of nitrogen, and arginase (also known as arginine amidohydrolase, ARGAH) is responsible for catalyse of arginine into ornithine and urea in plants. In this study, the impact of AtARGAHs on abiotic stress response was investigated by manipulating AtARGAHs expression. In the knockout mutants of AtARGAHs, enhanced tolerances were observed to multiple abiotic stresses including water deficit, salt, and freezing stresses, while AtARGAH1- and AtARGAH2-overexpressing lines exhibited reduced abiotic stress tolerances compared to the wild type. Consistently, the enhanced tolerances were confirmed by the changes of physiological parameters including electrolyte leakage, water loss rate, stomatal aperture, and survival rate. Interestingly, the direct downstream products of arginine catabolism including polyamines and nitric oxide (NO) concentrations significantly increased in the AtARGAHs-knockout lines, but decreased in overexpressing lines under control conditions. Additionally, the AtARGAHs-overexpressing and -knockout lines displayed significantly reduced relative arginine (% of total free amino acids) relative to the wild type. Similarly, reactive oxygen species accumulation was remarkably regulated by AtARGAHs under abiotic stress conditions, as shown from hydrogen peroxide (H2O2), superoxide radical () concentrations, and antioxidant enzyme activities. Taken together, this is the first report, as far as is known, to provide evidence that AtARGAHs negatively regulate many abiotic stress tolerances, at least partially, attribute to their roles in modulating arginine metabolism and reactive oxygen species accumulation. Biotechnological strategy based on manipulation of AtARGAHs expression will be valuable for future crop breeding. PMID:23378380

The calcium sensor GhCaM7 promotes cotton fiber elongation by modulating reactive oxygen species (ROS) production.

PubMed

Tang, Wenxin; Tu, Lili; Yang, Xiyan; Tan, Jiafu; Deng, Fenglin; Hao, Juan; Guo, Kai; Lindsey, Keith; Zhang, Xianlong

2014-04-01

Fiber elongation is the key determinant of fiber quality and output in cotton (Gossypium hirsutum). Although expression profiling and functional genomics provide some data, the mechanism of fiber development is still not well understood. Here, a gene encoding a calcium sensor, GhCaM7, was isolated based on its high expression level relative to other GhCaMs in fiber cells at the fast elongation stage. The level of expression of GhCaM7 in the wild-type and the fuzzless/lintless mutant correspond to the presence and absence, respectively, of fiber initials. Overexpressing GhCaM7 promotes early fiber elongation, whereas GhCaM7 suppression by RNAi delays fiber initiation and inhibits fiber elongation. Reactive oxygen species (ROS) play important roles in early fiber development. ROS induced by exogenous hydrogen peroxide (H2 O2 ) and Ca(2+) starvation promotes early fiber elongation. GhCaM7 overexpression fiber cells show increased ROS concentrations compared with the wild-type, while GhCaM7 RNAi fiber cells have reduced concentrations. Furthermore, we show that H2 O2 enhances Ca(2+) influx into the fiber and feedback-regulates the expression of GhCaM7. We conclude that GhCaM7, Ca(2+) and ROS are three important regulators involved in early fiber elongation. GhCaM7 might modulate ROS production and act as a molecular link between Ca(2+) and ROS signal pathways in early fiber development. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

The crude extract of Corni Fructus induces apoptotic cell death through reactive oxygen species-modulated pathways in U-2 OS human osteosarcoma cells.

PubMed

Liao, Ching-Lung; Hsu, Shu-Chun; Yu, Chien-Chih; Yang, Jai-Sing; Tang, Nou-Ying; Wood, Wellington Gibson; Lin, Jaung-Geng; Chung, Jing-Gung

2014-09-01

Crude extract of Corni Fructus (CECF) has been used in Traditional Chinese medicine for the treatment of different diseases for hundreds of years. The purpose of this study was to investigate the cytotoxic effects of CECF on U-2 OS human osteosarcoma cells. Flow cytometry was used for measuring the percentage of viable cells, cell-cycle distribution, apoptotic cells in sub-G1 phase, reactive oxygen species (ROS), Ca(2+) levels, and mitochondrial membrane potential (ΔΨm ). Comet assay and 4'-6-diamidino-2-phenylindole staining were used for examining DNA damage and condensation. Western blotting was used to examine apoptosis-associated protein levels in U-2 OS cells after exposed to CECF. Immunostaining and confocal laser system microscope were used to examine protein translocation after CECF incubation. CECF decreased the percentage of viability, induced DNA damage and DNA condensation, G₀/G₁ arrest, and apoptosis in U-2 OS cells. CECF-stimulated activities of caspase-8, caspase-9, and caspase-3, ROS, and Ca(2+) production, decreased ΔΨm levels of in U-2 OS cells. CECF increased protein levels of caspase-3, caspase-9, Bax, cytochrome c, GRP78, AIF, ATF-6α, Fas, TRAIL, p21, p27, and p16 which were associated with cell-cycle arrest and apoptosis. These findings suggest that CECF triggers apoptosis in U-2 OS cells via ROS-modulated caspase-dependent and -independent pathways. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Redox signaling in acute oxygen sensing.

PubMed

Gao, Lin; González-Rodríguez, Patricia; Ortega-Sáenz, Patricia; López-Barneo, José

2017-08-01

Acute oxygen (O 2 ) sensing is essential for individuals to survive under hypoxic conditions. The carotid body (CB) is the main peripheral chemoreceptor, which contains excitable and O 2 -sensitive glomus cells with O 2 -regulated ion channels. Upon exposure to acute hypoxia, inhibition of K + channels is the signal that triggers cell depolarization, transmitter release and activation of sensory fibers that stimulate the brainstem respiratory center to produce hyperventilation. The molecular mechanisms underlying O 2 sensing by glomus cells have, however, remained elusive. Here we discuss recent data demonstrating that ablation of mitochondrial Ndufs2 gene selectively abolishes sensitivity of glomus cells to hypoxia, maintaining responsiveness to hypercapnia or hypoglycemia. These data suggest that reactive oxygen species and NADH generated in mitochondrial complex I during hypoxia are signaling molecules that modulate membrane K + channels. We propose that the structural substrates for acute O 2 sensing in CB glomus cells are "O 2 -sensing microdomains" formed by mitochondria and neighboring K + channels in the plasma membrane. Copyright © 2017. Published by Elsevier B.V.

Streptococcus mutans NADH oxidase lies at the intersection of overlapping regulons controlled by oxygen and NAD+ levels.

PubMed

Baker, J L; Derr, A M; Karuppaiah, K; MacGilvray, M E; Kajfasz, J K; Faustoferri, R C; Rivera-Ramos, I; Bitoun, J P; Lemos, J A; Wen, Z T; Quivey, R G

2014-06-01

NADH oxidase (Nox, encoded by nox) is a flavin-containing enzyme used by the oral pathogen Streptococcus mutans to reduce diatomic oxygen to water while oxidizing NADH to NAD(+). The critical nature of Nox is 2-fold: it serves to regenerate NAD(+), a carbon cycle metabolite, and to reduce intracellular oxygen, preventing formation of destructive reactive oxygen species (ROS). As oxygen and NAD(+) have been shown to modulate the activity of the global transcription factors Spx and Rex, respectively, Nox is potentially poised at a critical junction of two stress regulons. In this study, microarray data showed that either addition of oxygen or loss of nox resulted in altered expression of genes involved in energy metabolism and transport and the upregulation of genes encoding ROS-metabolizing enzymes. Loss of nox also resulted in upregulation of several genes encoding transcription factors and signaling molecules, including the redox-sensing regulator gene rex. Characterization of the nox promoter revealed that nox was regulated by oxygen, through SpxA, and by Rex. These data suggest a regulatory loop in which the roles of nox in reduction of oxygen and regeneration of NAD(+) affect the activity levels of Spx and Rex, respectively, and their regulons, which control several genes, including nox, crucial to growth of S. mutans under conditions of oxidative stress. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production.

PubMed Central

Wenisch, C; Parschalk, B; Weiss, A; Zedwitz-Liebenstein, K; Hahsler, B; Wenisch, H; Georgopoulos, A; Graninger, W

1996-01-01

Flow cytometry was used to study phagocytic function (uptake of fluorescein isothiocyanate-labeled bacteria) and release of reactive oxygen products (dihydrorhodamine 123 converted to rhodamine 123) following phagocytosis by neutrophil granulocytes of heparinized whole blood treated with adrenaline, noradrenaline, dopamine, dobutamine, or orciprenaline. Reduced neutrophil phagocytosis and reactive oxygen production were seen at 12 micrograms of adrenaline per liter (72% each compared with control values); at 120 micrograms of noradrenaline (72% each), dobutamine (83 and 80%, respectively), and orciprenaline (81 and 80%, respectively) per liter; and at 100 micrograms of dopamine per liter (66 and 70%) (P < 0.05 for all). At these dosages, neutrophil chemotaxis was reduced to < 50% of control values for all catecholamines. Treatment with catecholamines at lower dosages had no significant effect on phagocytosis or generation of reactive oxygen products or chemotaxis. The phagocytic capacity of granulocytes was related to the generation of reactive oxygen products (r = 0.789; P < 0.05). The results demonstrate that catecholamines have a suppressive effect on the response of phagocytic cells to bacterial pathogens at high therapeutic levels in blood. PMID:8807207

Engineering of Pyranose Dehydrogenase for Increased Oxygen Reactivity

PubMed Central

Krondorfer, Iris; Lipp, Katharina; Brugger, Dagmar; Staudigl, Petra; Sygmund, Christoph; Haltrich, Dietmar; Peterbauer, Clemens K.

2014-01-01

Pyranose dehydrogenase (PDH), a member of the GMC family of flavoproteins, shows a very broad sugar substrate specificity but is limited to a narrow range of electron acceptors and reacts extremely slowly with dioxygen as acceptor. The use of substituted quinones or (organo)metals as electron acceptors is undesirable for many production processes, especially of food ingredients. To improve the oxygen reactivity, site-saturation mutagenesis libraries of twelve amino acids around the active site of Agaricus meleagris PDH were expressed in Saccharomyces cerevisiae. We established high-throughput screening assays for oxygen reactivity and standard dehydrogenase activity using an indirect Amplex Red/horseradish peroxidase and a DCIP/D-glucose based approach. The low number of active clones confirmed the catalytic role of H512 and H556. Only one position was found to display increased oxygen reactivity. Histidine 103, carrying the covalently linked FAD cofactor in the wild-type, was substituted by tyrosine, phenylalanine, tryptophan and methionine. Variant H103Y was produced in Pichia pastoris and characterized and revealed a five-fold increase of the oxygen reactivity. PMID:24614932

Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins

PubMed Central

2017-01-01

As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these proteins, they share common mechanistic grounds. An open-shell transition metal like iron or copper is employed to interact with O2 and its derived intermediates such as hydrogen peroxide to afford a variety of metal–oxygen intermediates. These reactive intermediates, including metal-superoxo, -(hydro)peroxo, and high-valent metal–oxo species, are the basis for the various biological functions of O2-utilizing metalloproteins. Collectively, these processes are called oxygen activation. Much of our understanding of the reactivity of these reactive intermediates has come from the study of heme-containing proteins and related metalloporphyrin compounds. These studies not only have deepened our understanding of various functions of heme proteins, such as O2 storage and transport, degradation of reactive oxygen species, redox signaling, and biological oxygenation, etc., but also have driven the development of bioinorganic chemistry and biomimetic catalysis. In this review, we survey the range of O2 activation processes mediated by heme proteins and model compounds with a focus on recent progress in the characterization and reactivity of important iron–oxygen intermediates. Representative reactions initiated by these reactive intermediates as well as some context from prior decades will also be presented. We will discuss the fundamental mechanistic features of these transformations and delineate the underlying structural and electronic factors that contribute to the spectrum of reactivities that has been observed in nature as well as those that have been invented using these paradigms. Given the recent developments in biocatalysis for non-natural chemistries and the renaissance of radical chemistry in organic synthesis, we envision that new enzymatic and synthetic transformations will emerge based on the radical processes mediated by metalloproteins and their synthetic analogs. PMID:29286645

Comparison of two strategies for detection of reactive oxygen species

NASA Astrophysics Data System (ADS)

Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

2014-09-01

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

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

PubMed

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

2014-09-01

Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown to play protective roles against chronic alcohol consumption. Although excessive reactive oxygen species (ROS) production in macrophages is considered one of the critical events for ethanol-induced damage in various target tissues, the effect of adiponectin on ethanol-induced ROS production is not clearly understood. In the present study, we investigated the effect of globular adiponectin (gAcrp) on ethanol-induced ROS production and the potential mechanisms underlying these effects of gAcrp in macrophages. Here we demonstrated that gAcrp prevented ethanol-induced ROS production in both RAW 264.7 macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced increase in the expression of NADPH oxidase subunits, including Nox2 and p22(phox), via modulation of nuclear factor-κB pathway. Furthermore, pretreatment with compound C, a selective inhibitor of AMPK, or knockdown of AMPK by small interfering RNA restored suppression of ethanol-induced ROS production and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2 expression, suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and activation of NADPH oxidase by gAcrp. Taken together, these results demonstrate that globular adiponectin prevents ethanol-induced ROS production, at least in part, via modulation of NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in the suppression of ethanol-induced NADPH oxidase activation by gAcrp in macrophages. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Reactive oxygen metabolites (ROMs) as an index of oxidative stress in obstructive sleep apnea patients.

PubMed

Christou, Kostas; Markoulis, Nikolaos; Moulas, Anargyros N; Pastaka, Chaido; Gourgoulianis, Kostantinos I

2003-09-01

Obstructive sleep apnea syndrome (OSA) is accompanied by oxygen desaturation and arousal from sleep. Free oxygen radicals are highly reactive molecules which could be produced by the OSA phenomenon of hypoxia/reoxygenation: cyclical alterations of arterial oxygen saturation with oxygen desaturation developing in response to apneas followed by resumption of oxygen saturation during hyperventilation. On the basis of these considerations, it was hypothesized that OSA may be linked to increased oxidative stress. Twenty-six participants gave an interview during which a physician asked them about their age, smoking habits, and symptoms such as excessive daytime sleepiness and snoring. Physical examination and polysomnography were performed during their hospitalization. Reactive oxygen metabolites (ROMs) were measured in blood samples by the diacron reactive oxygen metabolites (D-ROM) test. Twenty-one out of 26 subjects had an apnea/hypopnea index greater than 5 (OSA group). The measurement of free radicals was high in OSA patients. Furthermore, ROMs values in OSA patients were linearly correlated with the apnea/hypopnea index (R = 0.426; p = 0.042). The predictive value of a positive D-ROM test is 81%. ROMs were elevated in patients with OSA. When OSA was severe, similarly the value of ROMs in blood samples was enhanced, and the probable underlying mechanism for these events is the hypoxia/reoxygenation phenomenon.

Copper-Exchanged Zeolite L Traps Oxygen

NASA Technical Reports Server (NTRS)

Sharma, Pramod K.; Seshan, Panchalam K.

1991-01-01

Brief series of simple chemical treatments found to enhance ability of zeolite to remove oxygen from mixture of gases. Thermally stable up to 700 degrees C and has high specific surface area which provides high capacity for adsorption of gases. To increase ability to adsorb oxygen selectively, copper added by ion exchange, and copper-exchanged zeolite reduced with hydrogen. As result, copper dispersed atomically on inner surfaces of zeolite, making it highly reactive to oxygen, even at room temperature. Reactivity to oxygen even greater at higher temperatures.

Antioxidant modulation in response to heavy metal induced oxidative stress in Cladophora glomerata.

PubMed

Murugan, K; Harish, S R

2007-11-01

The present investigation was carried out to study the induction of oxidative stress subjected to heavy metal environment. Lipoperoxides showed positive correlation at heavy metal accumulation sites indicating the tissue damage resulting from the reactive oxygen species and resulted in unbalance to cellular redox status. The high activities of ascorbate peroxidase and superoxide dismutase probably counter balance this oxidative stress. Glutathione and soluble phenols decreased, whereas dehydroascorbate content increased in the algae from polluted sites. The results suggested that alga responded to heavy metals effectively by antioxidant compounds and scavenging enzymes.

Introduction to the thematic minireview series on redox-active protein modifications and signaling.

PubMed

Banerjee, Ruma

2013-09-13

The dynamics of redox metabolism necessitate cellular strategies for sensing redox changes and for responding to them. A common mechanism for receiving and transmitting redox changes is via reversible modifications of protein cysteine residues. A plethora of cysteine modifications have been described, including sulfenylation, glutathionylation, and disulfide formation. These post-translational modifications have the potential to alter protein structure and/or function and to modulate cellular processes ranging from division to death and from circadian rhythms to secretion. The focus of this thematic minireview series is cysteine modifications in response to reactive oxygen and nitrogen species.

Up-regulation of A1M/α1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage.

PubMed

Olsson, Magnus G; Allhorn, Maria; Larsson, Jörgen; Cederlund, Martin; Lundqvist, Katarina; Schmidtchen, Artur; Sørensen, Ole E; Mörgelin, Matthias; Akerström, Bo

2011-01-01

During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.

Purinergic Modulation of Spinal Neuroglial Maladaptive Plasticity Following Peripheral Nerve Injury.

PubMed

Cirillo, Giovanni; Colangelo, Anna Maria; Berbenni, Miluscia; Ippolito, Vita Maria; De Luca, Ciro; Verdesca, Francesco; Savarese, Leonilde; Alberghina, Lilia; Maggio, Nicola; Papa, Michele

2015-12-01

Modulation of spinal reactive gliosis following peripheral nerve injury (PNI) is a promising strategy to restore synaptic homeostasis. Oxidized ATP (OxATP), a nonselective antagonist of purinergic P2X receptors, was found to recover a neuropathic behavior following PNI. We investigated the role of intraperitoneal (i.p.) OxATP treatment in restoring the expression of neuronal and glial markers in the mouse spinal cord after sciatic spared nerve injury (SNI). Using in vivo two-photon microscopy, we imaged Ca(2+) transients in neurons and astrocytes of the dorsal horn of spinal cord at rest and upon right hind paw electrical stimulation in sham, SNI, and OxATP-treated mice. Neuropathic behavior was investigated by von Frey and thermal plantar test. Glial [glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1)] and GABAergic [vesicular GABA transporter (vGAT) and glutamic acid decarboxylase 65/76 (GAD65/67)] markers and glial [glutamate transporter (GLT1) and GLAST] and neuronal amino acid [EAAC1, vesicular glutamate transporter 1 (vGLUT1)] transporters have been evaluated. In SNI mice, we found (i) increased glial response, (ii) decreased glial amino acid transporters, and (iii) increased levels of neuronal amino acid transporters, and (iv) in vivo analysis of spinal neurons and astrocytes showed a persistent increase of Ca(2+) levels. OxATP administration reduced glial activation, modulated the expression of glial and neuronal glutamate/GABA transporters, restored neuronal and astrocytic Ca(2+) levels, and prevented neuropathic behavior. In vitro studies validated that OxATP (i) reduced levels of reactive oxygen species (ROS), (ii) reduced astrocytic proliferation, (iii) increase vGLUT expression. All together, these data support the correlation between reactive gliosis and perturbation of the spinal synaptic homeostasis and the role played by the purinergic system in modulating spinal plasticity following PNI.

Base excision repair, the redox environment and therapeutic implications.

PubMed

Storr, S J; Woolston, C M; Martin, S G

2012-01-01

Control of redox homeostasis is crucial for a number of cellular processes with deregulation leading to a number of serious consequences including oxidative damage such induction of DNA base lesions. The DNA lesions caused by oxidative damage are principally repaired by the base excision repair (BER) pathway. Pharmacological inhibition of BER is becoming an increasingly active area of research with the emergence of PARP inhibitors in cancer therapy. The redox status of the cell is modulated by a number of systems, including a large number of anti-oxidant enzymes who function in the control of superoxide and hydrogen peroxide, and ultimately in the release of the damaging hydroxyl radical. Here we provide an overview of reactive oxygen species (ROS) production and its modulation by antioxidant enzymes. The review also discusses the effect of ROS on the BER pathway, particularly in relation to cancer. Finally, as the modulation of the redox environment is of interest in cancer therapy, with certain agents having the potential to reverse chemo- and radiotherapy resistance or treat therapy related toxicity, we discuss redox modulating agents currently under development.

Nitrite therapy after cardiac arrest reduces ROS generation, improves cardiac and neurological function and enhances survival via reversible inhibition of mitochondrial complex I

PubMed Central

Dezfulian, Cameron; Shiva, Sruti; Alekseyenko, Aleksey; Pendyal, Akshay; Beiser, DG; Munasinghe, Jeeva P.; Anderson, Stasia A.; Chesley, Christopher F.; Hoek, TL Vanden; Gladwin, Mark T.

2009-01-01

Background Three-fourths of cardiac arrest survivors die prior to hospital discharge or suffer significant neurological injury. Excepting therapeutic hypothermia and revascularization, no novel therapies have been developed that improve survival or cardiac and neurological function after resuscitation. Nitrite (NO2−) increases cellular resilience to focal ischemia-reperfusion injury in multiple organs. We hypothesized that nitrite therapy may improve outcomes after the unique global ischemia-reperfusion insult of cardiopulmonary arrest. Methods and Results We developed a mouse model of cardiac arrest characterized by 12-minutes of normothermic asystole and a high cardiopulmonary resuscitation (CPR) rate. In this model, global ischemia and CPR was associated with blood and organ nitrite depletion, reversible myocardial dysfunction, impaired alveolar gas exchange, neurological injury and an approximate 50% mortality. A single low dose of intravenous nitrite (50 nmol=1.85 μmol/kg=0.13 mg/kg) compared to blinded saline placebo given at CPR initiation with epinephrine improved cardiac function, survival and neurological outcomes. From a mechanistic standpoint, nitrite treatment restored intracardiac nitrite and increased S-nitrosothiol levels, decreased pathological cardiac mitochondrial oxygen consumption due to reactive oxygen species formation and prevented oxidative enzymatic injury via reversible specific inhibition of respiratory chain complex I. Conclusion Nitrite therapy after resuscitation from 12-minutes of asystole rapidly and reversibly modulated mitochondrial reactive oxygen species generation during early reperfusion, limiting acute cardiac dysfunction and death, as well as neurological impairment in survivors. PMID:19704094

Ethylene negatively regulates transcript abundance of ROP-GAP rheostat-encoding genes and affects apoplastic reactive oxygen species homeostasis in epicarps of cold stored apple fruits

PubMed Central

Zermiani, Monica; Zonin, Elisabetta; Nonis, Alberto; Begheldo, Maura; Ceccato, Luca; Vezzaro, Alice; Baldan, Barbara; Trentin, Annarita; Masi, Antonio; Pegoraro, Marco; Fadanelli, Livio; Teale, William; Palme, Klaus; Quintieri, Luigi; Ruperti, Benedetto

2015-01-01

Apple (Malus×domestica Borkh) fruits are stored for long periods of time at low temperatures (1 °C) leading to the occurrence of physiological disorders. ‘Superficial scald’ of Granny Smith apples, an economically important ethylene-dependent disorder, was used as a model to study relationships among ethylene action, the regulation of the ROP-GAP rheostat, and maintenance of H2O2 homeostasis in fruits during prolonged cold exposure. The ROP-GAP rheostat is a key module for adaptation to low oxygen in Arabidopsis through Respiratory Burst NADPH Oxidase Homologs (RBOH)-mediated and ROP GTPase-dependent regulation of reactive oxygen species (ROS) homeostasis. Here, it was shown that the transcriptional expression of several components of the apple ROP-GAP machinery, including genes encoding RBOHs, ROPs, and their ancillary proteins ROP-GEFs and ROP-GAPs, is coordinately and negatively regulated by ethylene in conjunction with the progressive impairment of apoplastic H2O2 homeostatic levels. RNA sequencing analyses showed that several components of the known ROP- and ROS-associated transcriptional networks are regulated along with the ROP-GAP rheostat in response to ethylene perception. These findings may extend the role of the ROP-GAP rheostat beyond hypoxic responses and suggest that it may be a functional regulatory node involved in the integration of ethylene and ROS signalling pathways in abiotic stress. PMID:26428066

The Synergistic Effect of Proteins and Reactive Oxygen Species on Electrochemical Behaviour of 316L Stainless Steel for Biomedical Applications

NASA Astrophysics Data System (ADS)

Simionescu, N.; Benea, L.; Dumitrascu, V. M.

2018-06-01

The stainless steels, especially 316L type is the most used metallic biomaterials for biomedical applications due to their good biocompatibility, low price, excellent corrosion resistance, availability, easy processing and high strength. Due to these favorable properties 316L stainless steel has become the most attractive biomaterial for dental implants, stents and orthopedic implants. However an implant material in the human body is exposed to an action effect of other molecules, including proteins (such as albumin) and reactive oxygen species (such as hydrogen peroxide - H2O2 ) produced by bacteria and immune cells. In the literature there are few studies to follow the effect of proteins and reactive oxygen species on 316L stainless steel used as implant material and are still unclear. The degree of corrosion resistance is the first criterion in the use of a metallic biomaterial in the oral or body environment. The aim of this research work is to investigate the influence of proteins (albumin) and reactive oxygen species (H2O2 ) in combination, taking into account the synergistic effect of these two factors on 316L stainless steel. Albumin is present in the body near implants and reactive oxygen species could appear in inflammatory processes as well. The study shows that the presence of albumin and reactive species influences the corrosion resistance of 316L stainless steel in biological solutions. In this research work the corrosion behavior of 316L stainless steel is analyzed by electrochemical methods such as: open circuit potential (OCP), Electrochemical Impedance Spectroscopy (EIS). It was found that, the electrochemical results are in a good agreement with micro photographs taken before and after corrosion assays. The albumin and reactive oxygen species have influence on 316L stainless steel behavior.

The importance of sphingolipids and reactive oxygen species in cardiovascular development.

PubMed

de Faria Poloni, Joice; Chapola, Henrique; Feltes, Bruno César; Bonatto, Diego

2014-06-01

The heart is the first organ in the embryo to form. Its structural and functional complexity is the result of a thorough developmental program, where sphingolipids play an important role in cardiogenesis, heart maturation, angiogenesis, the regulation of vascular tone and vessel permeability. Sphingolipids are necessary for signal transduction and membrane microdomain formation. In addition, recent evidence suggests that sphingolipid metabolism is directly interconnected to the modulation of oxidative stress. However, cardiovascular development is highly sensitive to excessive reactive species production, and disturbances in sphingolipid metabolism can lead to abnormal development and cardiac disease. Therefore, in this review, we address the molecular link between sphingolipids and oxidative stress, connecting these pathways to cardiovascular development and cardiovascular disease. © 2014 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Iron-mediated redox modulation in neural plasticity

PubMed Central

Muñoz, Pablo

2012-01-01

The role of iron in brain physiology has focused on the neuropathological, effects due to iron-induced oxidative stress. However, our recent work has established a physiological relationship between the iron-mediated oxidative modification and normal neuronal function. Our results obtained from hippocampal neurons, suggest that iron-generated reactive species oxygen (ROS) are involved in calcium signaling initiated by stimulation of NMDA receptors. This signal is amplified by ryanodine receptors (RyR), a redox- sensitive calcium channel, allowing the phosphorylation and nuclear translocation of ERK1/2. Furthermore, using electrophysiological approaches, we showed that iron is required for basal synaptic transmission and full expression of long-term potentiation, a type of synaptic plasticity. Our data combined suggest that the oxidative effect of iron is critical to activate processes that are downstream of NMDAR activation. Finally, due to the high reactivity of DNA with iron-generated ROS, we hypothesize an additional function of iron in gene regulation. PMID:22808323

Early bioelectric activities mediate redox-modulated regeneration

PubMed Central

Ferreira, Fernando; Luxardi, Guillaume; Reid, Brian

2016-01-01

Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (JI) during regeneration. Depletion of ROS mimics the altered TEP and JI observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H2O2) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and JI reversal. H2O2 is therefore necessary for and sufficient to induce regeneration and to regulate TEP and JI. Epistasis assays show that voltage-gated Na+ channels act downstream of H2O2 to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration. PMID:27827821

Rab7-a novel redox target that modulates inflammatory pain processing.

PubMed

Kallenborn-Gerhardt, Wiebke; Möser, Christine V; Lorenz, Jana E; Steger, Mirco; Heidler, Juliana; Scheving, Reynir; Petersen, Jonas; Kennel, Lea; Flauaus, Cathrin; Lu, Ruirui; Edinger, Aimee L; Tegeder, Irmgard; Geisslinger, Gerd; Heide, Heinrich; Wittig, Ilka; Schmidtko, Achim

2017-07-01

Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.

Are soluble factors relevant for polymorphonuclear leukocyte dysregulation in septicemia?

PubMed Central

Wenisch, C; Graninger, W

1995-01-01

Polymorphonuclear leukocytes (PMNs) of twelve patients with gram-negative septicemia exhibited a decreased capacity to phagocytize Escherichia coli and generate reactive oxygen products which normalized within 7 days of treatment. Ex vivo exchange of plasma from age-, sex-, and blood-group-identical normal controls resulted in an increase of both phagocytic capacity and reactive oxygen intermediate generation in PMNs of septicemic patients and transiently reduced phagocytosis and reactive oxygen intermediate production in PMNs of normal controls. These results suggest that extrinsic factors are crucial for PMN function. PMID:7697538

Rosacea, Reactive Oxygen Species, and Azelaic Acid

PubMed Central

2009-01-01

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

Rosacea, reactive oxygen species, and azelaic Acid.

PubMed

Jones, David A

2009-01-01

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

Thermal characterization of TiCxOy thin films

NASA Astrophysics Data System (ADS)

Fernandes, A. C.; Vaz, F.; Gören, A.; Junge, K. H.; Gibkes, J.; Bein, B. K.; Macedo, F.

2008-01-01

Thermal wave characterization of thin films used in industrial applications can be a useful tool, not just to get information on the films' thermal properties, but to get information on structural-physical parameters, e.g. crystalline structure and surface roughness, and on the film deposition conditions, since the thermal film properties are directly related to the structural-physical parameters and to the deposition conditions. Different sets of TiCXOY thin films, deposited by reactive magnetron sputtering on steel, have been prepared, changing only one deposition parameter at a time. Here, the effect of the oxygen flow on the thermal film properties is studied. The thermal waves have been measured by modulated IR radiometry, and the phase lag data have been interpreted using an Extremum method by which the thermal coating parameters are directly related to the values and modulation frequencies of the relative extrema of the inverse calibrated thermal wave phases. Structural/morphological characterization has been done using X-ray diffraction (XRD) and atomic force microscopy (AFM). The characterization of the films also includes thickness, hardness, and electric resistivity measurements. The results obtained so far indicate strong correlations between the thermal diffusivity and conductivity, on the one hand, and the oxygen flow on the other hand.

Roles of oxyanions in promoting the partial oxidation of styrene on Ag(110): nitrate, carbonate, sulfite, and sulfate.

PubMed

Zhou, Ling; Madix, Robert J

2010-11-02

The promotion roles of nitrate, carbonate, sulfite, and sulfate in oxidation of styrene on Ag(110) have been studied by means of temperature-programmed reaction spectroscopy (TPRS) and X-ray photoelectron spectroscopy (XPS). While isolated nitrate leads only to the secondary oxidation of styrene, a surface co-covered by nitrate, oxygen, and 0.1 ML cesium promotes a low-temperature epoxidation pathway. XPS indicates that adsorbed surface oxygen is the oxidant in this selective reaction pathway, and, though it affects the reactivity of the surface oxygen, nitrate is a spectator. Carbonate acts as an oxygen transfer agent and exhibits similar reactivity and selectivity as an oxidant for styrene as does atomic oxygen on Ag(110). The reactivities of sulfite and sulfate are strongly dependent on their surface structures, the c(6 × 2) sulfite showing the capacity to transfer oxygen to styrene.

Flavodiiron proteins Flv1 and Flv3 enable cyanobacterial growth and photosynthesis under fluctuating light.

PubMed

Allahverdiyeva, Yagut; Mustila, Henna; Ermakova, Maria; Bersanini, Luca; Richaud, Pierre; Ajlani, Ghada; Battchikova, Natalia; Cournac, Laurent; Aro, Eva-Mari

2013-03-05

Cyanobacterial flavodiiron proteins (FDPs; A-type flavoprotein, Flv) comprise, besides the β-lactamase-like and flavodoxin domains typical for all FDPs, an extra NAD(P)H:flavin oxidoreductase module and thus differ from FDPs in other Bacteria and Archaea. Synechocystis sp. PCC 6803 has four genes encoding the FDPs. Flv1 and Flv3 function as an NAD(P)H:oxygen oxidoreductase, donating electrons directly to O2 without production of reactive oxygen species. Here we show that the Flv1 and Flv3 proteins are crucial for cyanobacteria under fluctuating light, a typical light condition in aquatic environments. Under constant-light conditions, regardless of light intensity, the Flv1 and Flv3 proteins are dispensable. In contrast, under fluctuating light conditions, the growth and photosynthesis of the Δflv1(A) and/or Δflv3(A) mutants of Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120 become arrested, resulting in cell death in the most severe cases. This reaction is mainly caused by malfunction of photosystem I and oxidative damage induced by reactive oxygen species generated during abrupt short-term increases in light intensity. Unlike higher plants that lack the FDPs and use the Proton Gradient Regulation 5 to safeguard photosystem I, the cyanobacterial homolog of Proton Gradient Regulation 5 is shown not to be crucial for growth under fluctuating light. Instead, the unique Flv1/Flv3 heterodimer maintains the redox balance of the electron transfer chain in cyanobacteria and provides protection for photosystem I under fluctuating growth light. Evolution of unique cyanobacterial FDPs is discussed as a prerequisite for the development of oxygenic photosynthesis.

Reagents that block neuronal death from Huntington's disease also curb oxidative stress.

PubMed

Valencia, Antonio; Sapp, Ellen; Reeves, Patrick B; Alexander, Jonathan; Masso, Nicholas; Li, Xueyi; Kegel, Kimberly B; DiFiglia, Marian

2012-01-04

Patients with Huntington's disease suffer severe neuronal loss and signs of oxidative damage in the brain. Previously we found that primary neurons from embryonic cortex of mice bearing the Huntington's disease mutation (140 glutamines inserted into exon 1 of huntingtin) showed higher levels of reactive oxygen species before cell death. Here, we treated mutant neurons with known neuroprotective agents and determined the effects on neuronal survival and levels of reactive oxygen species. Primary neurons were exposed to the neurotrophin, brain derived neurotrophic factor, the antioxidant N-acetyl-cysteine or a specific inhibitor of glycogen synthase kinase 3-β, SB216763. Each reagent increased the survival of the mutant neurons compared with untreated mutant neurons and also reduced the levels of reactive oxygen species to levels of wild-type neurons. These results suggest that reducing the levels of reactive oxygen species may be necessary to protect neurons with the Huntington's disease mutation from cell death.

Redox signaling in remote ischemic preconditioning-induced cardioprotection: Evidences and mechanisms.

PubMed

Singh, Lovedeep; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

2017-08-15

Reactive oxygen species are the reactive molecules that are derived from molecular oxygen and play an important role as redox signaling molecules to confer cardioprotection. Various scientists have demonstrated the key role of redox signaling in cardioprotection by showing a transient increase in their levels during remote ischemic preconditioning (RIPC) phase. The transient increase in reactive oxygen species levels during remote preconditioning phase may take place either through activation of K ATP channels or through increased nitric oxide (NO) production. A transient increase in reactive oxygen species during preconditioning may also increase the expression of heat shock proteins (HSP), the level of antioxidant enzymes and decrease the expression of inflammatory genes (Egr-1) during ischemia-reperfusion phase to confer cardioprotection. The present review describes the role of redox signaling in RIPC-induced cardioprotective effect with possible mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Space Station evolution study oxygen loop closure

NASA Technical Reports Server (NTRS)

Wood, M. G.; Delong, D.

1993-01-01

In the current Space Station Freedom (SSF) Permanently Manned Configuration (PMC), physical scars for closing the oxygen loop by the addition of oxygen generation and carbon dioxide reduction hardware are not included. During station restructuring, the capability for oxygen loop closure was deferred to the B-modules. As such, the ability to close the oxygen loop in the U.S. Laboratory module (LAB A) and the Habitation A module (HAB A) is contingent on the presence of the B modules. To base oxygen loop closure of SSF on the funding of the B-modules may not be desirable. Therefore, this study was requested to evaluate the necessary hooks and scars in the A-modules to facilitate closure of the oxygen loop at or subsequent to PMC. The study defines the scars for oxygen loop closure with impacts to cost, weight and volume and assesses the effects of byproduct venting. In addition, the recommended scenarios for closure with regard to topology and packaging are presented.

[Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

PubMed

Ren, Si-Hua; He, Yu-Xin; Ma, Yi-Ran; Jin, Jing-Chun; Kang, Dan

2016-02-01

To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

CADDIS Volume 2. Sources, Stressors and Responses: Dissolved Oxygen

EPA Pesticide Factsheets

Introduction to the dissolved oxygen module, when to list dissolved oxygen as a candidate cause, ways to measure dissolved oxygen, simple and detailed conceptual model diagrams for dissolved oxygen, references for the dissolved oxygen module.

Frequency of polymorphism -262 c/t in catalase gene and oxidative damage in Slovak children with bronchial asthma.

PubMed

Babusikova, Eva; Jesenak, Milos; Evinova, Andrea; Banovcin, Peter; Dobrota, Dusan

2013-12-01

Bronchial asthma is a complex disease in which genetic factors, environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression. If antioxidant mechanisms fail, reactive oxygen species damage the biomolecules followed by progression of the disease. Catalase is one of the most important endogenous enzymatic antioxidants. In the present study, we examined the hypothesis that increased oxidative damage and polymorphism in the CAT gene (-262 promoter region, C/T) are associated with childhood bronchial asthma. Genotyping of the polymorphisms in the CAT gene in healthy (249) and asthmatic children (248) was performed using polymerase chain reaction-restriction fragment length polymorphism. Markers of oxidative damage: content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children. The TT genotype of catalase was more frequent among the asthmatic patients (22.6%) than in healthy children (4.8%) (odds ratio=5.63; 95% confidence interval=2.93-10.81, P<.001). The amount of sulfhydryl groups decreased significantly and conversely, the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene. These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children. Genetic variation of enzymatic antioxidants may modulate disease risk. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Reactive oxygen species and nitric oxide are involved in polyamine-induced growth inhibition in wheat plants.

PubMed

Recalde, Laura; Vázquez, Analía; Groppa, María D; Benavides, María Patricia

2018-03-06

Polyamines (PAs) produce H 2 O 2 and nitric oxide (NO) during their normal catabolism and modulate plant growth and development. To explore the biochemical basis of PAs-induced growth inhibition in Triticum aestivum L seedlings, we examined the role of O 2 ·- , H 2 O 2 or NO in shoot and root development. Although all PA treatments resulted in a variable reduction of root and shoot elongation, spermine (Spm) caused the greater inhibition in a similar way to that observed with the NO donor, sodium nitroprusside (SNP). In both cases, O 2 ·- production was completely blocked whereas H 2 O 2 formation was high in the root apex under SNP or Spm treatments. Catalase recovered root and shoot growth in SNP but not in Spm-treated plants, revealing the involvement of H 2 O 2 in SNP-root length reduction. The addition of the NO scavenger, cPTIO, restored root length in SNP- or Spm-treated plants, respectively, and partially recovered O 2 ·- levels, compared to the plants exposed to PAs or SNP without cPTIO. A strong correlation was observed between root growth restoration and O 2 ·- accumulation after treating roots with SNP + aminoguanidine, a diamine oxidase inhibitor, and with SNP + 1,8-diaminoctane, a polyamine oxidase inhibitor, confirming the essential role of O 2 ·- formation for root growth and the importance of the origin and level of H 2 O 2 . The differential modulation of wheat growth by PAs through reactive oxygen species or NO is discussed. Graphical abstract Polyamines, nitric oxide and ROS interaction in plants during plant growth.

Autophagy modulators sensitize prostate epithelial cancer cell lines to TNF-alpha-dependent apoptosis.

PubMed

Giampietri, Claudia; Petrungaro, Simonetta; Padula, Fabrizio; D'Alessio, Alessio; Marini, Elettra Sara; Facchiano, Antonio; Filippini, Antonio; Ziparo, Elio

2012-11-01

TNF-alpha levels in prostate cancer correlate with the extent of disease and are significantly elevated in the metastatic stage. TNF receptor superfamily controls two distinct signalling cascades, leading to opposite effects, i.e. apoptosis and survival; in prostate cancer TNF-alpha-mediated signalling induces cell survival and resistance to therapy. The apoptosis of prostate epithelial cancer cells LNCaP and PC3 was investigated upon treatment with the autophagy inhibitor 3-methyladenine and the autophagy inducer rapamycin, in combination with TNF-alpha. Cells were exposed to these molecules for 18, 24 and 48 h. Autophagy was assessed via LC3 Western blot analysis; propidium iodide and TUNEL stainings followed by flow cytometry or caspase-8 and caspase-3 activation assays were performed to evaluate apoptosis. TNF-alpha-induced apoptosis was potentiated by 3-methyladenine in the androgen-responsive LNCaP cells, whereas no effect was observed in the androgen-insensitive PC3 cells. Interestingly such pro-apoptosis effect in LNCaP cells was associated with reduced c-Flip levels through proteasomal degradation via increased reactive oxygen species production and p38 activation; such c-Flip reduction was reversed in the presence of either the proteasome inhibitor MG132 or the reactive oxygen species scavenger N-acetyl-cysteine. Conversely in PC3 but not in LNCaP cells, rapamycin stimulated TNF-alpha-dependent apoptosis; such effect was associated with reduced c-Flip promoter activity and FoxO3a activation. We conclude that TNF-alpha-induced apoptosis may be potentiated, in prostate cancer epithelial cells, through autophagy modulators. Increased sensitivity to TNF-alpha-dependent apoptosis correlates with reduced c-Flip levels which are consequent to a post-transcriptional and a transcriptional mechanism in LNCaP and PC3 cells respectively.

Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase.

PubMed

Jeng, Jiiang-Huei; Chen, Shiao-Yun; Liao, Chang-Hui; Tung, Yuan-Yii; Lin, Bor-Ru; Hahn, Liang-Jiunn; Chang, Mei-Chi

2002-05-01

There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.

Temperature induced modulation of lipid oxidation and lipid accumulation in palmitate-mediated 3T3-L1 adipocytes and 3T3-L1 adipocytes.

PubMed

Lin, Xiaofen; Li, Yi; Leung, Polly Hangmei; Li, Jiashen; Hu, Junyan; Liu, Xuan; Li, Zhi

2016-05-01

Human skin temperature can vary widely depending on anatomical location and ambient temperature. It is also known that local changes in skin and subcutaneous temperature can affect fat metabolism. This study aimed to explore the potential effects of surrounding thermal environment on fat by investigating cell viability, lipid oxidation, and lipid accumulation in 3T3-L1 adipocytes and palmitate-treated adipocytes after 4h incubation. No significant differences of viability in 3T3-L1 adipocytes were detected under different temperature conditions. Despite no significant increase being observed under warm temperature (39°C) conditions, a similarly significant suppression of intracellular reactive oxygen species (ROS) and lipid peroxidation were found in 3T3-L1 adipocytes and palmitate-treated adipocytes under 4h exposure to cooler temperatures of 31-33°C (P<0.01). ROS, chemically reactive molecules containing oxygen, are currently understood to be a major contributor to oxidantive stress in obesity. Additionally, cooler temperatures (31-33°C) could improve the size of lipid droplets in 3T3-L1 adipocytes (P<0.01), but no significant effect was generated by temperature change on lipid droplets in palmitate-treated adipocytes. In the palmitate-induced adiposity model, although excessive ROS and lipid peroxidation has been attenuated by temperature decrease (P<0.01), it still does not positively modulate lipid droplet size (P>0.05) and remedy the palmitate damage induced cell death (P<0.01). These findings provide preliminary support for potential interventions based on temperature manipulation for cell metabolism of adipocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Salicylic acid alleviates aluminum toxicity in soybean roots through modulation of reactive oxygen species metabolism

NASA Astrophysics Data System (ADS)

Liu, Ning; Song, Fengbin; Zhu, Xiancan; You, Jiangfeng; Yang, Zhenming; Li, Xiangnan

2017-11-01

As an important signal molecule, salicylic acid (SA) improves plant tolerance to aluminum (Al) stress. The objective of this study was to investigate the effects of exogenous SA application on the dynamics of endogenous SA and reactive oxygen species in soybean (Glycine max L.) exposed to Al stress. The roots of soybean seedlings were exposed to a combination of AlCl3 (30 μM) and SA (10 μM)/PAC (100 μM, paclobutrazol, SA biosynthesis inhibitor) for 3, 6, 9 and 12 h. Al stress induced an increase in endogenous SA concentration in a time-dependent manner, also verified by the up-regulated expression of GmNPR1, an SA-responsive gene. Al stress increased the activities of phenylalanine ammonia-lyase (PAL) and benzoic acid 2-hydroxylase (BA2H), and the contents of SA, O2- and malondialdehyde (MDA) in the root apex. The application of exogenous SA increased PAL and BA2H, and reduced O2- and MDA contents in soybean roots under Al stress. PAC inhibited the SA induced increase in BA2H activity. In addition, the SA application resulted in a rapid increase in hydrogen peroxide (H2O2) concentration under Al stress, followed by a sharp decrease. Compared with the plants exposed to Al alone, Al+SA plants possessed higher activities of superoxide dismutase, peroxidase and ascorbate peroxidase, and lower catalase activity, indicating that SA alleviated Al-induced oxidative damage. These results suggested that PAL and BA2H were involved in Al-induced SA production and showed that SA alleviated the adverse effects of Al toxicity by modulating the cellular H2O2 level and the antioxidant enzyme activities in the soybean root apex.

Cytosolic Calcium, hydrogen peroxide, and related gene expression and protein modulation in Arabidopsis thaliana cell cultures respond immediately to altered gravitation: Parabolic flight data

NASA Astrophysics Data System (ADS)

Hampp, Ruediger; Hausmann, Niklas; Neef, Maren; Fengler, Svenja

Callus cell cultures of Arabidopsis thaliana (cv. Columbia) were exposed to parabolic flights in order to assess molecular short-term responses to altered gravity fields. Using transgenic cell lines, hydrogen peroxide and cytosolic Ca2+ were continuously monitored. In parallel, the metabolism of samples was chemically quenched (RNAlater, Ambion, for RNA; acid/base for NADPH, NADP) at typical stages of a parabola (1g before pull up; end of pull up (1.8 g), end of microgravity (µg, 20 sec), and end of pull out (1.8 g)). Cells exhibited an increase of both Ca2+ and hydrogen peroxide with the onset of µg, and a decline thereafter. This behaviour was accompanied by a decrease of the NADPH/NADP redox ratio, indicating a Ca2+-dependent activation of a NADPH oxidase. Microarray analyses revealed concomitant expression profiles. At the end of the microgravity phase, 396 transcripts were specifically up-, while 485 were down-regulated. Up-regulation was dominated by Ca2+- and ROS(reactive oxygen species)-related gene products. The same material was also used for the analysis of phosphopeptides by 2D SDS PAGE. Relevant spots were identified by liquid chromatography-MS. With the exception of a chaperone (HSP 70-3), hypergravity (1.8 g) and microgravity modified different sets of proteins. These are partly involved in primary metabolism (glycolysis, gluconeogenesis, citrate cycle) and detoxification of reactive oxygen species. Taken together, these data show that both gene expression and protein modulation jointly respond within seconds to alterations in the gravity field, with a focus on metabolic adaptation, signalling and control of ROS.

Involvement of glutathione/glutathione S-transferase antioxidant system in butyrate-inhibited vascular smooth muscle cell proliferation.

PubMed

Ranganna, Kasturi; Mathew, Omana P; Yatsu, Frank M; Yousefipour, Zivar; Hayes, Barbara E; Milton, Shirlette G

2007-11-01

Vascular smooth muscle cell (VSMC) proliferation is an important etiological factor in vascular proliferative diseases such as primary atherosclerosis, hypertension, arterial and in-stent restenosis, and transplant vasculopathy. Our studies established that butyrate, a bacterial fermentation product of dietary fiber and a chromatin modulator, is a potent inhibitor of VSMC proliferation. The cardiovascular health benefits of a high-fiber diet, the principle source of butyrate in the body, have been known for a long time, however, very little is known about the antiatherogenic potential of butyrate. Because oxidative stress plays an important role in the pathogenesis of atherosclerosis, we examined involvement of the glutathione/glutathione S-transferase (GST) antioxidant system in butyrate's inhibition of VSMC proliferation. Treatment of proliferating VSMCs with butyrate leads to the induction of several GSTs. Interestingly, our study also demonstrated the nuclear localization of GST-P1 (GST-7-7), which is considered to be a cytosolic protein; this was demonstrated using immunostaining and was corroborated by western blotting. Also, the butyrate-induced antiproliferative action, and the induction of GST-P1 and its nuclear localization are downregulated when butyrate is withdrawn. Furthermore, assessment of intracellular glutathione levels reveals their augmentation by butyrate. Conversely, butyrate treatment reduces the levels of reactive oxygen species in VSMCs. Collectively, the butyrate-treatment-related increase in glutathione content, the reduction in reactive oxygen species, the upregulation of GST and the nuclear localization of GST-P1 in growth-arrested VSMCs imply that butyrate's antiproliferative action involves modulation of the cellular redox state. Thus, induction of the glutathione/GST antioxidant system appears to have other regulatory role(s) besides detoxification and regulation of the cellular redox state, for example, cell-cycle control and cell proliferation, which are both critical to atherogenesis.

Lipoic acid mitigates oxidative stress and recovers metabolic distortions in salt-stressed wheat seedlings by modulating ion homeostasis, the osmo-regulator level and antioxidant system.

PubMed

Gorcek, Zeynep; Erdal, Serkan

2015-11-01

Soil salinity is one of the most detrimental environmental factors affecting the growth of plants and limiting their agricultural productivity. This study investigated whether exogenous lipoic acid (LA) pretreatment plays a role in promoting salt tolerance in wheat seedlings. The seedlings were treated with LA (1.75 mmol L(-1)) and salt (100 mmol L(-1) NaCl) separately and a combination of them. Salt stress significantly reduced relative water content, leaf surface area, ribulose bisphosphate carboxylase expression, and chlorophyll content but increased the content of osmo-regulator protein, carbohydrates and proline. In addition, salinity led to an imbalance in the inorganic composition of wheat leaves. While it elevated Na(+) content compared to control, Ca content and K(+)/Na(+) ratio were reduced. Under saline conditions, despite increases in antioxidant enzyme activity and levels of antioxidant compounds (ascorbate and glutathione), the content of reactive oxygen species (superoxide anion, hydrogen peroxide) and malondialdehyde were higher than in control seedlings. LA significantly promoted osmo-regulator level and antioxidant enzyme activities compared to stressed seedlings alone. Also, it both increased levels of ascorbate and glutathione and regenerated their oxidised forms, thus contributing to maintaining cellular redox status. Similarly, LA prevented excessive accumulation of Na(+) and promoted K(+)/Na(+) ratio and Ca content. Reactive oxygen species content was significantly reduced, and the inhibitions in the above parameters markedly recovered. LA reduced salinity-induced oxidative damage and thus contributed to the growth and development of plants in saline soils by modulating ion homeostasis between plant and soil as well as in osmo-regulator content and antioxidant system. © 2014 Society of Chemical Industry.

Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells.

PubMed

Battisti, Federico; Napoletano, Chiara; Rahimi Koshkaki, Hassan; Belleudi, Francesca; Zizzari, Ilaria Grazia; Ruscito, Ilary; Palchetti, Sara; Bellati, Filippo; Benedetti Panici, Pierluigi; Torrisi, Maria Rosaria; Caracciolo, Giulio; Altieri, Fabio; Nuti, Marianna; Rughetti, Aurelia

2017-01-01

Dendritic cells (DCs) are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8 + T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs) enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS) accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

Redox signaling in cardiac myocytes

PubMed Central

Santos, Celio X.C.; Anilkumar, Narayana; Zhang, Min; Brewer, Alison C.; Shah, Ajay M.

2011-01-01

The heart has complex mechanisms that facilitate the maintenance of an oxygen supply–demand balance necessary for its contractile function in response to physiological fluctuations in workload as well as in response to chronic stresses such as hypoxia, ischemia, and overload. Redox-sensitive signaling pathways are centrally involved in many of these homeostatic and stress-response mechanisms. Here, we review the main redox-regulated pathways that are involved in cardiac myocyte excitation–contraction coupling, differentiation, hypertrophy, and stress responses. We discuss specific sources of endogenously generated reactive oxygen species (e.g., mitochondria and NADPH oxidases of the Nox family), the particular pathways and processes that they affect, the role of modulators such as thioredoxin, and the specific molecular mechanisms that are involved—where this knowledge is available. A better understanding of this complex regulatory system may allow the development of more specific therapeutic strategies for heart diseases. PMID:21236334

CADDIS Volume 2. Sources, Stressors and Responses: Dissolved Oxygen - Simple Conceptual Diagram

EPA Pesticide Factsheets

Introduction to the dissolved oxygen module, when to list dissolved oxygen as a candidate cause, ways to measure dissolved oxygen, simple and detailed conceptual model diagrams for dissolved oxygen, references for the dissolved oxygen module.

CADDIS Volume 2. Sources, Stressors and Responses: Dissolved Oxygen - Detailed Conceptual Diagram

EPA Pesticide Factsheets

Introduction to the dissolved oxygen module, when to list dissolved oxygen as a candidate cause, ways to measure dissolved oxygen, simple and detailed conceptual model diagrams for dissolved oxygen, references for the dissolved oxygen module.

Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous Wound Repair

PubMed Central

Modarressi, Ali; Pittet-Cuénod, Brigitte

2017-01-01

Our understanding of the role of oxygen in cell physiology has evolved from its long-recognized importance as an essential factor in oxidative metabolism to its recognition as an important player in cell signaling. With regard to the latter, oxygen is needed for the generation of reactive oxygen species (ROS), which regulate a number of different cellular functions including differentiation, proliferation, apoptosis, migration, and contraction. Data specifically concerning the role of ROS-dependent signaling in cutaneous wound repair are very limited, especially regarding wound contraction. In this review we provide an overview of the current literature on the role of molecular and reactive oxygen in the physiology of wound repair as well as in the pathophysiology and therapy of chronic wounds, especially under ischemic and hyperglycemic conditions. PMID:29036938

Reactive oxygen species: players in the cardiovascular effects of testosterone

PubMed Central

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

2015-01-01

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

Reciprocal Regulation of Reactive Oxygen Species and Phospho-CREB Regulates Voltage Gated Calcium Channel Expression during Mycobacterium tuberculosis Infection

PubMed Central

Selvakumar, Arti; Antony, Cecil; Singhal, Jhalak; Tiwari, Brijendra K.; Singh, Yogendra; Natarajan, Krishnamurthy

2014-01-01

Our previous work has demonstrated the roles played by L-type Voltage Gated Calcium Channels (VGCC) in regulating Mycobacterium tuberculosis (M. tb) survival and pathogenesis. Here we decipher mechanisms and pathways engaged by the pathogen to regulate VGCC expression in macrophages. We show that M. tb and its antigen Rv3416 use phospho-CREB (pCREB), Reactive Oxygen Species (ROS), Protein Kinase C (PKC) and Mitogen Activated Protein Kinase (MAPK) to modulate VGCC expression in macrophages. siRNA mediated knockdown of MyD88, IRAK1, IRAK2 or TRAF6 significantly inhibited antigen mediated VGCC expression. Inhibiting Protein Kinase C (PKC) or MEK-ERK1/2 further increased VGCC expression. Interestingly, inhibiting intracellular calcium release upregulated antigen mediated VGCC expression, while inhibiting extracellular calcium influx had no significant effect. siRNA mediated knockdown of transcription factors c-Jun, SOX5 and CREB significantly inhibited Rv3416 mediated VGCC expression. A dynamic reciprocal cross-regulation between ROS and pCREB was observed that in turn governed VGCC expression with ROS playing a limiting role in the process. Further dissection of the mechanisms such as the interplay between ROS and pCREB would improve our understanding of the regulation of VGCC expression during M. tb infection. PMID:24797940

Uncoupling proteins and the control of mitochondrial reactive oxygen species production.

PubMed

Mailloux, Ryan J; Harper, Mary-Ellen

2011-09-15

Reactive oxygen species (ROS), natural by-products of aerobic respiration, are important cell signaling molecules, which left unchecked can severely impair cellular functions and induce cell death. Hence, cells have developed a series of systems to keep ROS in the nontoxic range. Uncoupling proteins (UCPs) 1-3 are mitochondrial anion carrier proteins that are purported to play important roles in minimizing ROS emission from the electron transport chain. The function of UCP1 in this regard is highly contentious. However, UCPs 2 and 3 are generally thought to be activated by ROS or ROS by-products to induce proton leak, thus providing a negative feedback loop for mitochondrial ROS production. In our laboratory, we have not only confirmed that ROS activate UCP2 and UCP3, but also demonstrated that UCP2 and UCP3 are controlled by covalent modification by glutathione. Furthermore, the reversible glutathionylation is required to activate/inhibit UCP2 and UCP3, but not UCP1. Hence, our findings are consistent with the notion that UCPs 2 and 3 are acutely activated by ROS, which then directly modulate the glutathionylation status of the UCP to decrease ROS emission and participate in cell signaling mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Jin Sil; Lee, Sora; Yoo, Young Do, E-mail: ydy1130@korea.ac.kr

2014-08-08

Highlights: • Romo1 expression is required for constitutive nuclear DNA-binding activity of NF-κB. • Romo1 depletion suppresses tumor growth in vivo. • Romo1 presents a potential therapeutic target for diseases. - Abstract: Deregulation of nuclear factor-κB (NF-κB) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-κB activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclearmore » 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.« less

Mechano-stimulated modifications in the chloroplast antioxidant system and proteome changes are associated with cold response in wheat.

PubMed

Li, Xiangnan; Hao, Chenglong; Zhong, Jianwen; Liu, Fulai; Cai, Jian; Wang, Xiao; Zhou, Qin; Dai, Tingbo; Cao, Weixing; Jiang, Dong

2015-09-11

Mechanical wounding can cause morphological and developmental changes in plants, which may affect the responses to abiotic stresses. However, the mechano-stimulation triggered regulation network remains elusive. Here, the mechano-stimulation was applied at two different times during the growth period of wheat before exposing the plants to cold stress (5.6 °C lower temperature than the ambient temperature, viz., 5.0 °C) at the jointing stage. Results showed that mechano-stimulation at the Zadoks growth stage 26 activated the antioxidant system, and substantially, maintained the homeostasis of reactive oxygen species. In turn, the stimulation improved the electron transport and photosynthetic rate of wheat plants exposed to cold stress at the jointing stage. Proteomic and transcriptional analyses revealed that the oxidative stress defense, ATP synthesis, and photosynthesis-related proteins and genes were similarly modulated by mechano-stimulation and the cold stress. It was concluded that mechano-stimulated modifications of the chloroplast antioxidant system and proteome changes are related to cold tolerance in wheat. The findings might provide deeper insights into roles of reactive oxygen species in mechano-stimulated cold tolerance of photosynthetic apparatus, and be helpful to explore novel approaches to mitigate the impacts of low temperature occurring at critical developmental stages.

Dose Dependent Effects of Reactive Oxygen and Nitrogen Species on the Function of Neuronal Nitric Oxide Synthase

PubMed Central

Sun, Jian; Druhan, Lawrence J.; Zweier, Jay L.

2014-01-01

Reactive nitrogen species (RNS) and oxygen species (ROS) have been reported to modulate the function of nitric oxide synthase (NOS); however, the precise dosedependent effects of specific RNS and ROS on NOS function are unknown. Questions remain unanswered regarding whether pathophysiological levels of RNS and ROS alter NOS function, and if this alteration is reversible. We measured the effects of peroxynitrite (ONOO-), superoxide (O2.-), hydroxyl radical (.OH), and H2O2 on nNOS activity. The results showed that NO production was inhibited in a dose-dependent manner by all four oxidants, but only O2.- and ONOO- were inhibitory at pathophysiological concentrations (≤ 50 μM). Subsequent addition of tetrahydrobiopterin (BH4) fully restored activity after O2.- exposure, while BH4 partially rescued the activity decrease induced by the other three oxidants. Furthermore, treatment with either ONOO- or O2.- stimulated nNOS uncoupling with decreased NO and enhanced O2.- generation. Thus, nNOS is reversibly uncoupled by O2.- (≤ 50 μM), but irreversibly uncoupled and inactivated by ONOO-. Additionally, we observed that the mechanism by which oxidative stress alters nNOS activity involves not only BH4 oxidation, but also nNOS monomerization as well as possible degradation of the heme. PMID:18201545

α-Syntrophin stabilizes catalase to reduce endogenous reactive oxygen species levels during myoblast differentiation.

PubMed

Moon, Jae Yun; Choi, Su Jin; Heo, Cheol Ho; Kim, Hwan Myung; Kim, Hye Sun

2017-07-01

α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis. Two-photon microscopy imaging showed that excessive intracellular ROS accumulated during the differentiation of SNKD cells as compared with control cells. The formation of 4-hydroxynonenal adduct, a byproduct of lipid peroxidation during oxidative stress, significantly increased in differentiated SNKD myotubes and was dramatically reduced by epigallocatechin-3-gallate, a well-known ROS scavenger. Among antioxidant enzymes, catalase was significantly decreased during differentiation of SNKD cells without changes at the mRNA level. Of interest was the finding that the degradation of catalase was rescued by MG132, a proteasome inhibitor, in the SNKD cells. This study demonstrates a novel function of α-syntrophin. This protein plays an important role in the regulation of oxidative stress from endogenously generated ROS during myoblast differentiation by modulating the protein stability of catalase. © 2017 Federation of European Biochemical Societies.

Diisopropylamine dichloroacetate enhances radiosensitization in esophageal squamous cell carcinoma by increasing mitochondria-derived reactive oxygen species levels

PubMed Central

Yu, Decai; Mao, Qixing; Xia, Wenjie; Shi, Run; Wang, Jie; Xu, Lin

2016-01-01

Radiotherapy is generally applied in the treatment of esophageal squamous cell carcinoma (ESCC). However, the radioresistance of ESCC still remains an obstacle for the curative effect of this treatment. We hypothesized that diisopropylamine dichloroacetate (DADA), an inhibitor of pyruvate dehydrogenase kinase (PDK), might enhance radiosensitizationin resistant ESCC. The clonogenic survival assay revealed that DADA sensitized ESCC cells to radiotherapy in vitro; furthermore, the combination of DADA and radiotherapy increased the expression of γ-H2AX, which is a hallmark of DNA double-strand breaks. Arrest at G2/M phase as well as the induction of apoptosis of ESCC cells were also observed in the cells treated with the combination of DADA and radiotherapy. Notably, xenograft tumor growth was significantly suppressed in vivo by combined radiotherapy and DADA administration. It has been proven that glycolysis is highly correlated with radioresistance, which could be reversed by the shift from glycolysis to mitochondrial oxidation. In our present study, we found that DADA could modulate oxidative phosphorylation as well as increase the intracellular levels of reactive oxygen species (ROS). Collectively, we concluded that DADA-induced intracellular ROS accumulation was identified as the key factor of radiotherapy sensitization of ESCC. PMID:27626688

Calcium and Reactive Oxygen Species in Acute Pancreatitis: Friend or Foe?

PubMed Central

Booth, David M.; Mukherjee, Rajarshi; Sutton, Robert

2011-01-01

Abstract Significance Acute pancreatitis (AP) is a debilitating and, at times, lethal inflammatory disease, the causes and progression of which are incompletely understood. Disruption of Ca2+ homeostasis in response to precipitants of AP leads to loss of mitochondrial integrity and cellular necrosis. Recent Advances While oxidative stress has been implicated as a major player in the pathogenesis of this disease, its precise roles remain to be defined. Recent developments are challenging the perception of reactive oxygen species (ROS) as nonspecific cytotoxic agents, suggesting that ROS promote apoptosis that may play a vital protective role in cellular stress since necrosis is avoided. Critical Issues Fresh clinical findings have indicated that antioxidant treatment does not ameliorate AP and may actually worsen the outcome. This review explores the complex links between cellular Ca2+ signaling and the intracellular redox environment, with particular relevance to AP. Future Directions Recent publications have underlined the importance of both Ca2+ and ROS within the pathogenesis of AP, particularly in the determination of cell fate. Future research should elucidate the subtle interplay between Ca2+ and redox mechanisms that operate to modulate mitochondrial function, with a view to devising strategies for the preservation of organellar function. Antioxid. Redox Signal. 15, 2683–2698. PMID:21861696

Biological characterization of a novel in vitro cell irradiator

PubMed Central

Fowler, Tyler L.; Fisher, Michael M.; Bailey, Alison M.; Bednarz, Bryan P.

2017-01-01

To evaluate the overall robustness of a novel cellular irradiator we performed a series of well-characterized, dose-responsive assays to assess the consequences of DNA damage. We used a previously described novel irradiation system and a traditional 137Cs source to irradiate a cell line. The generation of reactive oxygen species was assessed using chloromethyl-H2DCFDA dye, the induction of DNA DSBs was observed using the comet assay, and the initiation of DNA break repair was assessed through γH2AX image cytometry. A high correlation between physical absorbed dose and biologic dose was seen for the production of intracellular reactive oxygen species, physical DNA double strand breaks, and modulation of the cellular double stand break pathway. The results compared favorably to irradiation with a traditional 137Cs source. The rapid, straightforward tests described form a reasonable approach for biologic characterization of novel irradiators. These additional testing metrics go beyond standard physics testing such as Monte Carlo simulation and thermo-luminescent dosimeter evaluation to confirm that a novel irradiator can produce the desired dose effects in vitro. Further, assessment of these biological metrics confirms that the physical handling of the cells during the irradiation process results in biologic effects that scale appropriately with dose. PMID:29232400

Ascorbate and α-tocopherol differentially modulate reactive oxygen species generation by neutrophils in response to FcγR and TLR agonists.

PubMed

Chapple, Iain Lc; Matthews, John B; Wright, Helen J; Scott, Ann E; Griffiths, Helen R; Grant, Melissa M

2013-01-01

Periodontitis, a ubiquitous chronic inflammatory disease, is associated with reduced antioxidant defences and neutrophil hyperactivity in terms of reactive oxygen species (ROS) generation. Its phenotype is thus characterized by oxidative stress. We have determined the effect of antioxidant micronutrients ascorbate and α-tocopherol on neutrophil ROS generation. Peripheral neutrophils from periodontally-healthy individuals (n = 20) were challenged with phorbol myristate acetate, IgG-opsonised Staphylococcus aureus, Fusobacterium nucleatum or PBS in the presence and absence of micronutrients (50 µM). Total and extracellular ROS were measured by luminol and isoluminol chemiluminescence respectively. Total and extracellular unstimulated, baseline ROS generation was unaffected by α-tocopherol, but inhibited by ascorbate and a combination of both micronutrients. Fcγ-receptor (Fcγ-R)-stimulated total or extracellular ROS generation was not affected by the presence of individual micronutrients. However, the combination significantly reduced extracellular FcγR-stimulated ROS release. Neither micronutrient inhibited TLR-stimulated total ROS, but the combination caused inhibition. Ascorbate and the micronutrient combination, but not α-tocopherol, inhibited extracellular ROS release by TLR-stimulated cells. Such micronutrient effects in vivo could be beneficial in reducing collateral tissue damage in chronic inflammatory diseases, such as periodontitis, while retaining immune-mediated neutrophil function.

Simulated digestion of Vitis vinifera seed powder: polyphenolic content and antioxidant properties.

PubMed

Janisch, Kerstin M; Olschläger, Carolin; Treutter, Dieter; Elstner, Erich F

2006-06-28

There is increasing evidence that reactive oxygen species arising from several enzymatic reactions are mediators of inflammatory events. Plant preparations have the potential for scavenging such reactive oxygen species. Flavans and procyanidins are bioavailable and stable during the process of cooking. This study used conditions that mimicked digestion of Vitis vinifera seed powder in the stomach (acidic preparation) and small intestine (neutral preparation). The flavonoids of these two preparations were released during simulated digestion and were determined with HPLC analysis. Biochemical model reactions relevant for the formation of reactive oxygen species in vivo at inflammatory sites were used to determine the antioxidant properties of the two preparations. The inhibition of the indicator reaction for the formation of reactive oxygen species represents a potential mechanism of the physiological activity of the corresponding preparation. The results of this work show clearly that the polyphenols released during the simulated digestion of the two preparations have good scavenging potential against superoxide radicals, hydroxyl radicals, and singlet oxygen. They protect low-density lipoprotein against copper-induced oxidation due to the copper-chelating properties and their chain-breaking abilities in lipid peroxidation.

COMPARATIVE ANALYSIS OF REACTIVE OXYGEN SPECIES IN HUMAN PLASMA AND BLOOD

EPA Science Inventory

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

NEW APPROACHES TO ESTIMATING INDIRECT PHOTOLYSIS RATES IN AQUATIC ENVIRONMENTS

EPA Science Inventory

Indirect photoreactions in aquatic environments are driven by reactive species, most of which are oxygen centered. Humic substances play an important role in photosensitizing the production of these reactive species, which include singlet molecular oxygen, superoxide ions, hydrog...

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

PubMed Central

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

2013-01-01

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

Mitochondrial stress controls the radiosensitivity of the oxygen effect: Implications for radiotherapy.

PubMed

Richardson, Richard B; Harper, Mary-Ellen

2016-04-19

It has been more than 60 years since the discovery of the oxygen effect that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. Yet the mechanisms underlying this principal tenet of radiobiology are poorly understood. Better understanding of the oxygen effect may explain difficulty in eliminating hypoxic tumor cells, a major cause of regrowth after therapy. Our analysis utilizes the Howard-Flanders and Alper formula, which describes the relationship of radiosensitivity with oxygen tension. Here, we assign and qualitatively assess the relative contributions of two important mechanisms. The first mechanism involves the emission of reactive oxygen species from the mitochondrial electron transport chain, which increases with oxygen tension. The second mechanism is related to an energy and repair deficit, which increases with hypoxia. Following a radiation exposure, the uncoupling of the oxidative phosphorylation system (proton leak) in mitochondria lowers the emission of reactive oxygen species which has implications for fractionated radiotherapy, particularly of hypoxic tumors. Our analysis shows that, in oxygenated tumor and normal cells, mitochondria, rather than the nucleus, are the primary loci of radiotherapy effects, especially for low linear energy transfer radiation. Therefore, the oxygen effect can be explained by radiation-induced effects in mitochondria that generate reactive oxygen species, which in turn indirectly target nuclear DNA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smed, T.; Andersson, G.

In this paper, damping of slow oscillations with active and reactive power modulation of HVDC-links is analyzed with the aim of gaining a physical insight into the problem. The analysis shows that active power modulation is efficient when applied to a short mass-scaled electrical distance from one of the swinging machines, and reactive power modulation is most efficient when there exists a well-defined power flow direction and the modulation is made at a point close to the electrical midpoint between the swinging machines. It is shown that the intuitively appealing feedback signals frequency and derivative of the voltage are appropriatemore » for active and reactive power modulation, respectively. The impact of the constraints imposed by the HVDC equations are analyzed, and it is determined when the implicit reactive power modulation resulting from constant [gamma] control may be detrimental for the damping.« less

BIOMONITORING OF REACTIVE OXYGEN SPECIES IN BIOLOGICAL FLUIDS

EPA Science Inventory

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

Investigation of the reactivity of organic materials in liquid oxygen

NASA Technical Reports Server (NTRS)

Chamberlain, D.; Irwin, K.; Kirshen, N.; Mill, T.; Stringham, R.

1970-01-01

Measurements of impact-ignition sensitivity and studies of the relative reactivity of t-butoxy and t-butyl peroxy radicals toward a variety of organic compounds reveal improved methods of selection of materials for safe use in a liquid oxygen environment.

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

EPA Science Inventory

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

Exposure to ultrafine particles, intracellular production of reactive oxygen species in leukocytes and altered levels of endothelial progenitor cells.

PubMed

Jantzen, Kim; Møller, Peter; Karottki, Dorina Gabriela; Olsen, Yulia; Bekö, Gabriel; Clausen, Geo; Hersoug, Lars-Georg; Loft, Steffen

2016-06-01

Exposure to particles in the fine and ultrafine size range has been linked to induction of low-grade systemic inflammation, oxidative stress and development of cardiovascular diseases. Declining levels of endothelial progenitor cells within systemic circulation have likewise been linked to progression of cardiovascular diseases. The objective was to determine if exposure to fine and ultrafine particles from indoor and outdoor sources, assessed by personal and residential indoor monitoring, is associated with altered levels of endothelial progenitor cells, and whether such effects are related to leukocyte-mediated oxidative stress. The study utilized a cross sectional design performed in 58 study participants from a larger cohort. Levels of circulating endothelial progenitor cells, defined as either late (CD34(+)KDR(+) cells) or early (CD34(+)CD133(+)KDR(+) cells) subsets were measured using polychromatic flow cytometry. We additionally measured production of reactive oxygen species in leukocyte subsets (lymphocytes, monocytes and granulocytes) by flow cytometry using intracellular 2',7'-dichlorofluoroscein. The measurements encompassed both basal levels of reactive oxygen species production and capacity for reactive oxygen species production for each leukocyte subset. We found that the late endothelial progenitor subset was negatively associated with levels of ultrafine particles measured within the participant residences and with reactive oxygen species production capacity in lymphocytes. Additionally, the early endothelial progenitor cell levels were positively associated with a personalised measure of ultrafine particle exposure and negatively associated with both basal and capacity for reactive oxygen species production in lymphocytes and granulocytes, respectively. Our results indicate that exposure to fine and ultrafine particles derived from indoor sources may have adverse effects on human vascular health. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A study of the free radical scavenging effects of Piper betle leaf extract in patients with vitiligo.

PubMed

Mitra, Sneha; Pati, Ayan Kumar; Manna, Alak; Ghosh, Arghyaprasun; Sen, Sumit; Chatterjee, Suparna; Chatterjee, Mitali

2017-01-01

Vitiligo is an idiopathic skin disease manifested by depigmented macules. It is characterised by melanocyte destruction, and redox imbalance is proposed to play a contributory role. The aim of this study was to analyze the effects of an ethanolic extract of Piper betle leaves on the generation of reactive oxygen species in erythrocytes sourced from vitiligo patients. The effect of Piper betle on the generation of reactive oxygen species in erythrocytes was measured by flow cytometry in patients with active and stable vitiligo versus healthy controls, using 5-(and-6)-chloromethyl-2'-7'-dichlorodihydrofluorescein diacetate. The generation of reactive oxygen species in erythrocytes was higher in patients with vitiligo (n = 23) compared to healthy controls (n = 18). The geometrical mean fluorescence channel was 23.05 ± 2.11 in patients versus 17.77 ± 1.79 in controls, P = 0.039. The levels of reactive oxygen species were higher in patients with active vitiligo. Treatment of erythrocytes with Piper betle in concentrations of 0.5 and 1.0 μg/ml significantly decreased the baseline levels of reactive oxygen species by 31.7% in healthy controls, and 47.6% and 44.3% in patients with active vitiligo, respectively. Piper betle effectively scavenged hydrogen peroxide, which was evident by a decrease in the geometrical mean fluorescence channel by 52.4% and 62.9% in healthy controls, and 45.0% and 57.0% in patients with active vitiligo. The study had a small sample size. Future studies should focus on evaluation of the antioxidant role of Piper betle at the lesional site. This pilot study indicates that patients with active vitiligo demonstrate enhanced generation of reactive oxygen species in erythrocytes, which was significantly reduced following ex vivo treatment with Piper betle.

Ethanol-induced erectile dysfunction and increased expression of pro-inflammatory proteins in the rat cavernosal smooth muscle are mediated by NADPH oxidase-derived reactive oxygen species.

PubMed

Leite, Letícia N; do Vale, Gabriel T; Simplicio, Janaina A; De Martinis, Bruno S; Carneiro, Fernando S; Tirapelli, Carlos R

2017-06-05

Ethanol consumption is associated with an increased risk of erectile dysfunction (ED), but the molecular mechanisms through which ethanol causes ED remain elusive. Reactive oxygen species are described as mediators of ethanol-induced cell toxicity/damage in distinctive tissues. The enzyme NADPH oxidase is the main source of reactive oxygen species in the endothelium and vascular smooth muscle cells and ethanol is described to increase NADPH oxidase activation and reactive oxygen species generation. This study evaluated the contribution of NADPH oxidase-derived reactive oxygen species to ethanol-induced ED, endothelial dysfunction and production of pro-inflammatory and redox-sensitive proteins in the rat cavernosal smooth muscle (CSM). Male Wistar rats were treated with ethanol (20% v/v) or ethanol plus apocynin (30mg/kg/day; p.o. gavage) for six weeks. Apocynin prevented both the decreased in acetylcholine-induced relaxation and intracavernosal pressure induced by ethanol. Ethanol increased superoxide anion (O 2 - ) generation and catalase activity in CSM, and treatment with apocynin prevented these responses. Similarly, apocynin prevented the ethanol-induced decreased of nitrate/nitrite (NOx), hydrogen peroxide (H 2 O 2 ) and SOD activity. Treatment with ethanol increased p47phox translocation to the membrane as well as the expression of Nox2, COX-1, catalase, iNOS, ICAM-1 and p65. Apocynin prevented the effects of ethanol on protein expression and p47phox translocation. Finally, treatment with ethanol increased both TNF-α production and neutrophil migration in CSM. The major new finding of this study is that NADPH oxidase-derived reactive oxygen species play a role on chronic ethanol consumption-induced ED and endothelial dysfunction in the rat CSM. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.

PubMed Central

Wenisch, C; Parschalk, B; Zedtwitz-Liebenstein, K; Weihs, A; el Menyawi, I; Graninger, W

1996-01-01

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose. PMID:8878577

Sensors, transmitters, and targets in mitochondrial oxygen shortage-a hypoxia-inducible factor relay story.

PubMed

Dehne, Nathalie; Brüne, Bernhard

2014-01-10

Cells sense and respond to a shortage of oxygen by activating the hypoxia-inducible transcription factors HIF-1 and HIF-2 and evoking adaptive responses. Mitochondria are at the center of a hypoxia sensing and responding relay system. Under normoxia, reactive oxygen species (ROS) and nitric oxide (NO) are HIF activators. As their individual flux rates determine their diffusion-controlled interaction, predictions how these radicals affect HIF appear context-dependent. Considering that the oxygen requirement for NO formation limits its role in activating HIF to conditions of ambient oxygen tension. Given the central role of mitochondrial complex IV as a NO target, especially under hypoxia, allows inhibition of mitochondrial respiration by NO to spare oxygen thus, raising the threshold for HIF activation. HIF targets seem to configure a feedback-signaling circuit aimed at gradually adjusting mitochondrial function. In hypoxic cancer cells, mitochondria redirect Krebs cycle intermediates to preserve their biosynthetic ability. Persistent HIF activation lowers the entry of electron-delivering compounds into mitochondria to reduce Krebs cycle fueling and β-oxidation, attenuates the expression of electron transport chain components, limits mitochondria biosynthesis, and provokes their removal by autophagy. Mitochondria can be placed central in a hypoxia sensing-hypoxia responding circuit. We need to determine to which extent and how mitochondria contribute to sense hypoxia, explore whether modulating their oxygen-consuming capacity redirects hypoxic responses in in vivo relevant disease conditions, and elucidate how the multiple HIF targets in mitochondria shape conditions of acute versus chronic hypoxia.

Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels.

PubMed

Fujita, Tomoyoshi; Hirooka, Kazuyuki; Nakamura, Takehiro; Itano, Toshifumi; Nishiyama, Akira; Nagai, Yukiko; Shiraga, Fumio

2012-06-26

To investigate the mechanism of the neuroprotective effects of the angiotensin II type 1 receptor (AT1-R) blocker against retinal ischemia-reperfusion injury in the rat. Retinal ischemia was induced by increasing intraocular pressure. Glutamate release from the rat retina and intravitreal PO(2) (partial pressure of oxygen) profiles were monitored during and after ischemia using a microdialysis biosensor and oxygen-sensitive microelectrodes. ELISA was used to measure changes in the expression of AT1-R. Retinal mRNA expressions of p47phox and p67phox were measured by real-time polymerase chain reaction. Reactive oxygen species (ROS) were measured using dihydroethidium. Administration of candesartan, which is an AT1-R blocker (ARB), suppressed ischemia-induced increases in the extracellular glutamate. Candesartan also attenuated the increase in intravitreal PO(2) during reperfusion. AT1-R expression peaked at 12 hours after reperfusion. Although there was an increase in the retinal mRNA expression of p47phox and p64phox at 12 hours after the reperfusion, administration of candesartan suppressed these expressions. The production of ROS that was detected at 12 hours after reperfusion was also suppressed by the administration of candesartan or apocynin. NADPH oxidase-mediated ROS production increased at 12 hours after reperfusion. Candesartan may protect neurons by decreasing extracellular glutamate immediately after reperfusion and by attenuating oxidative stress via a modulation of the AT1-R signaling that occurs during ischemic insult.

Polyoxygenated steroids from the gorgonian Menella woodin with capabilities to modulate ROS levels in macrophages at response to LPS.

PubMed

Tu, Vu A; Lyakhova, Ekaterina G; Diep, Chau N; Kalinovsky, Anatoly I; Dmitrenok, Pavel S; Cuong, Nguyen X; Thanh, Nguyen V; Menchinskaya, Ekaterina S; Pislyagin, Evgeny A; Nam, Nguyen H; Kiem, Phan V; Stonik, Valentin A; Minh, Chau V

2015-12-01

Four new polyoxygenated sterol derivatives (1-4) along with the compounds (5-7) previously known from other biological sources were isolated from the gorgonian Menella woodin, collected from the Vietnamese waters. Structures of 1-4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses as well as comparison with those reported in literature data. Compounds 1, 4, and 6 decrease the production of reactive oxygen species (ROS) by the murine macrophages of RAW 264.7 line at induction by endotoxic lipopolysaccharide (LPS) from Escherichia coli. Copyright © 2015 Elsevier Inc. All rights reserved.

Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

PubMed

Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

2015-04-20

Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

PubMed Central

Moreno-Beltrán, Blas; Guerra-Castellano, Alejandra; Del Conte, Rebecca; García-Mauriño, Sofía M.; Díaz-Moreno, Sofía; González-Arzola, Katiuska; Santos-Ocaña, Carlos; Velázquez-Campoy, Adrián; De la Rosa, Miguel A.; Turano, Paola; Díaz-Moreno, Irene

2017-01-01

Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methyl-l-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects. PMID:28348229

Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.

PubMed

Bou Sleiman, Maroun S; Osman, Dani; Massouras, Andreas; Hoffmann, Ary A; Lemaitre, Bruno; Deplancke, Bart

2015-07-27

Gut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.

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

EPA Science Inventory

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

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

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine.

PubMed

Cortese-Krott, Miriam M; Koning, Anne; Kuhnle, Gunter G C; Nagy, Peter; Bianco, Christopher L; Pasch, Andreas; Wink, David A; Fukuto, Jon M; Jackson, Alan A; van Goor, Harry; Olson, Kenneth R; Feelisch, Martin

2017-10-01

Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

Oxygen radicals as key mediators in neurological disease: fact or fiction?

PubMed

Halliwell, B

1992-01-01

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radicals and other reactive oxygen species are frequently proposed to be involved in the pathology of several neurological disorders. Criteria for establishing such involvement are presented. Development of new methods for measuring oxidative damage should enable elucidation of the precise role of reactive oxygen species in neurological disorders.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

The activation of molecular O 2as 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 O 2activation 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 O 2dissociation, 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 O 2dissociationmore » 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 O 2dissociation 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lu-Cun; Friend, C. M.; Fushimi, Rebecca

2016-01-01

The activation of molecular O 2as 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 O 2activation 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 O 2dissociation, 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 O 2dissociationmore » 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 O 2dissociation 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.« less

Ethylene negatively regulates transcript abundance of ROP-GAP rheostat-encoding genes and affects apoplastic reactive oxygen species homeostasis in epicarps of cold stored apple fruits.

PubMed

Zermiani, Monica; Zonin, Elisabetta; Nonis, Alberto; Begheldo, Maura; Ceccato, Luca; Vezzaro, Alice; Baldan, Barbara; Trentin, Annarita; Masi, Antonio; Pegoraro, Marco; Fadanelli, Livio; Teale, William; Palme, Klaus; Quintieri, Luigi; Ruperti, Benedetto

2015-12-01

Apple (Malus×domestica Borkh) fruits are stored for long periods of time at low temperatures (1 °C) leading to the occurrence of physiological disorders. 'Superficial scald' of Granny Smith apples, an economically important ethylene-dependent disorder, was used as a model to study relationships among ethylene action, the regulation of the ROP-GAP rheostat, and maintenance of H2O2 homeostasis in fruits during prolonged cold exposure. The ROP-GAP rheostat is a key module for adaptation to low oxygen in Arabidopsis through Respiratory Burst NADPH Oxidase Homologs (RBOH)-mediated and ROP GTPase-dependent regulation of reactive oxygen species (ROS) homeostasis. Here, it was shown that the transcriptional expression of several components of the apple ROP-GAP machinery, including genes encoding RBOHs, ROPs, and their ancillary proteins ROP-GEFs and ROP-GAPs, is coordinately and negatively regulated by ethylene in conjunction with the progressive impairment of apoplastic H2O2 homeostatic levels. RNA sequencing analyses showed that several components of the known ROP- and ROS-associated transcriptional networks are regulated along with the ROP-GAP rheostat in response to ethylene perception. These findings may extend the role of the ROP-GAP rheostat beyond hypoxic responses and suggest that it may be a functional regulatory node involved in the integration of ethylene and ROS signalling pathways in abiotic stress. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Mechanisms of Resistance to Photodynamic Therapy

PubMed Central

Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

2013-01-01

Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain

PubMed Central

Selivanov, Vitaly A.; Votyakova, Tatyana V.; Pivtoraiko, Violetta N.; Zeak, Jennifer; Sukhomlin, Tatiana; Trucco, Massimo; Roca, Josep; Cascante, Marta

2011-01-01

Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD+ reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC. PMID:21483483

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

EPA Science Inventory

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

Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions☆

PubMed Central

Mailloux, Ryan J.; Jin, Xiaolei; Willmore, William G.

2013-01-01

Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling. PMID:24455476

Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions.

PubMed

Mailloux, Ryan J; Jin, Xiaolei; Willmore, William G

2014-01-01

Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling.

Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

PubMed

Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed

2012-10-01

Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.

Transient heat and mass transfer analysis in a porous ceria structure of a novel solar redox reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chandran, RB; Bader, R; Lipinski, W

2015-06-01

Thermal transport processes are numerically analyzed for a porous ceria structure undergoing reduction in a novel redox reactor for solar thermochemical fuel production. The cylindrical reactor cavity is formed by an array of annular reactive elements comprising the porous ceria monolith integrated with gas inlet and outlet channels. Two configurations are considered, with the reactor cavity consisting of 10 and 20 reactive elements, respectively. Temperature dependent boundary heat fluxes are obtained on the irradiated cavity wall by solving for the surface radiative exchange using the net radiation method coupled to the heat and mass transfer model of the reactive element.more » Predicted oxygen production rates are in the range 40-60 mu mol s(-1) for the geometries considered. After an initial rise, the average temperature of the reactive element levels off at 1660 and 1680 K for the two geometries, respectively. For the chosen reduction reaction rate model, oxygen release continues after the temperature has leveled off which indicates that the oxygen release reaction is limited by chemical kinetics and/or mass transfer rather than by the heating rate. For a fixed total mass of ceria, the peak oxygen release rate is doubled for the cavity with 20 reactive elements due to lower local oxygen partial pressure. (C) 2015 Elsevier Masson SAS. All rights reserved.« less

Biochemical Oxygen Demand and Dissolved Oxygen. Training Module 5.105.2.77.

ERIC Educational Resources Information Center

Kirkwood Community Coll., Cedar Rapids, IA.

This document is an instructional module package prepared in objective form for use by an instructor familiar with the azide modification of the Winkler dissolved oxygen test and the electronic dissolved oxygen meter test procedures for determining the dissolved oxygen and the biochemical oxygen demand of a wastewater sample. Included are…

Temperature stress effects in Bemisia tabaci (Hemiptera: Aleyrodidae) type B whiteflies

USDA-ARS?s Scientific Manuscript database

Oxidative stress occurs in response to changes in the redox equilibiurm, which may be caused by increases in reactive oxygen species (ROS), a decrease in antioxidant protection or failure of cells to repair oxidative damage. ROS are either free radicals, reactive molecules containing oxygen atoms or...

Response of the ascorbate-glutathione cycle to storage temperature in carambola fruit

USDA-ARS?s Scientific Manuscript database

The generation of reactive oxygen species (ROS) is considered to be a primary event under a variety of stress conditions. It has been generally accepted that reactive oxygen produced under stress is a detrimental factor, which causes lipid peroxidation, enzyme inactivation, and oxidative damage to D...

Eicosanoids up-regulate production of reactive oxygen species by NADPH-dependent oxidase in Spodoptera exigua phagocytic hemocytes

USDA-ARS?s Scientific Manuscript database

Eicosanoids mediate cellular immune responses in insects, including phagocytosis of invading microbes. Phagocytosis entails two major steps, the internalization of microbes and the subsequent killing of them via formation of reactive oxygen species (ROS). Here, we posed the hypothesis that eicosanoi...

An innovative coupling between column leaching and oxygen consumption tests to assess behavior of contaminated marine dredged sediments.

PubMed

Couvidat, Julien; Benzaazoua, Mostafa; Chatain, Vincent; Zhang, Fan; Bouzahzah, Hassan

2015-07-01

Contaminated dredged sediments are often considered hazardous wastes, so they have to be adequately managed to avoid leaching of pollutants. The mobility of inorganic contaminants is a major concern. Metal sulfides (mainly framboïdal pyrite, copper, and zinc sulfides) have been investigated in this study as an important reactive metal-bearing phase sensitive to atmospheric oxygen action. An oxygen consumption test (OC-Test) has been adapted to assess the reactivity of dredged sediments when exposed to atmospheric oxygen. An experimental column set-up has been developed allowing the coupling between leaching and oxygen consumption test to investigate the reactivity of the sediment. This reactivity, which consisted of sulfide oxidation, was found to occur for saturation degree between 60 and 90 % and until the 20th testing week, through significant sulfates releases. These latter were assumed to come from sulfide oxidation in the first step of the test, then probably from gypsum dissolution. Confrontation results of OC-Test and leachate quality shows that Cu was well correlated to sulfates releases, which in turn, leads to Ca and Mg dissolution (buffer effect). Cu, and mostly Zn, was associated to organic matter, phyllosilicates, and other minerals through organo-clay complexes. This research confirmed that the OC-Test, originally developed for mine tailings, could be a useful tool in the dredged sediment field which can allow for intrinsic characterization of reactivity of a material suspected to readily reacting with oxygen and for better understanding of geochemical processes that affect pollutants behavior, conversion, and transfer in the environment.

The Nitrification Inhibitor Methyl 3-(4-Hydroxyphenyl)Propionate Modulates Root Development by Interfering with Auxin Signaling via the NO/ROS Pathway1

PubMed Central

Liu, Yangyang; Wang, Ruling; Zhang, Ping

2016-01-01

Methyl 3-(4-hydroxyphenyl)propionate (MHPP) is a root exudate that functions as a nitrification inhibitor and as a modulator of the root system architecture (RSA) by inhibiting primary root (PR) elongation and promoting lateral root formation. However, the mechanism underlying MHPP-mediated modulation of the RSA remains unclear. Here, we report that MHPP inhibits PR elongation in Arabidopsis (Arabidopsis thaliana) by elevating the levels of auxin expression and signaling. MHPP induces an increase in auxin levels by up-regulating auxin biosynthesis, altering the expression of auxin carriers, and promoting the degradation of the auxin/indole-3-acetic acid family of transcriptional repressors. We found that MHPP-induced nitric oxide (NO) production promoted reactive oxygen species (ROS) accumulation in root tips. Suppressing the accumulation of NO or ROS alleviated the inhibitory effect of MHPP on PR elongation by weakening auxin responses and perception and by affecting meristematic cell division potential. Genetic analysis supported the phenotype described above. Taken together, our results indicate that MHPP modulates RSA remodeling via the NO/ROS-mediated auxin response pathway in Arabidopsis. Our study also revealed that MHPP significantly induced the accumulation of glucosinolates in roots, suggesting the diverse functions of MHPP in modulating plant growth, development, and stress tolerance in plants. PMID:27217493

A study of the oxygen dynamics in a reactive Ar/O2 high power impulse magnetron sputtering discharge using an ionization region model

NASA Astrophysics Data System (ADS)

Lundin, D.; Gudmundsson, J. T.; Brenning, N.; Raadu, M. A.; Minea, T. M.

2017-05-01

The oxygen dynamics in a reactive Ar/O2 high power impulse magnetron sputtering discharge has been studied using a new reactive ionization region model. The aim has been to identify the dominating physical and chemical reactions in the plasma and on the surfaces of the reactor affecting the oxygen plasma chemistry. We explore the temporal evolution of the density of the ground state oxygen molecule O 2 ( X 1 Σg - ) , the singlet metastable oxygen molecules O 2 ( a 1 Δ g ) and O 2 ( b 1 Σ g ) , the oxygen atom in the ground state O(3P), the metastable oxygen atom O(1D), the positive ions O2 + and O+, and the negative ion O-. We furthermore investigate the reaction rates for the gain and loss of these species. The density of atomic oxygen increases significantly as we move from the metal mode to the transition mode, and finally into the compound (poisoned) mode. The main gain rate responsible for the increase is sputtering of atomic oxygen from the oxidized target. Both in the poisoned mode and in the transition mode, sputtering makes up more than 80% of the total gain rate for atomic oxygen. We also investigate the possibility of depositing stoichiometric TiO2 in the transition mode.

Early bioelectric activities mediate redox-modulated regeneration.

PubMed

Ferreira, Fernando; Luxardi, Guillaume; Reid, Brian; Zhao, Min

2016-12-15

Reactive oxygen species (ROS) and electric currents modulate regeneration; however, the interplay between biochemical and biophysical signals during regeneration remains poorly understood. We investigate the interactions between redox and bioelectric activities during tail regeneration in Xenopus laevis tadpoles. We show that inhibition of NADPH oxidase-mediated production of ROS, or scavenging or blocking their diffusion into cells, impairs regeneration and consistently regulates the dynamics of membrane potential, transepithelial potential (TEP) and electric current densities (J I ) during regeneration. Depletion of ROS mimics the altered TEP and J I observed in the non-regenerative refractory period. Short-term application of hydrogen peroxide (H 2 O 2 ) rescues (from depleted ROS) and induces (from the refractory period) regeneration, TEP increase and J I reversal. H 2 O 2 is therefore necessary for and sufficient to induce regeneration and to regulate TEP and J I Epistasis assays show that voltage-gated Na + channels act downstream of H 2 O 2 to modulate regeneration. Altogether, these results suggest a novel mechanism for regeneration via redox-bioelectric orchestration. © 2016. Published by The Company of Biologists Ltd.

Chemical waves in the O2 + H2 reaction on a Rh(111) surface alloyed with nickel. II. Photoelectron spectroscopy and microscopy

NASA Astrophysics Data System (ADS)

Smolinsky, Tim; Homann, Mathias; von Boehn, Bernhard; Gregoratti, Luca; Amati, Matteo; Al-Hada, Mohamed; Sezen, Hikmet; Imbihl, Ronald

2018-04-01

Chemical waves in the H2 + O2 reaction on a Rh(111) surface alloyed with Ni [ΘNi < 1.5 monolayers (ML)] have been investigated in the 10-7 and 10-6 mbar range at T = 773 K using scanning photoelectron microscopy and x-ray photoelectron spectroscopy as in situ methods. The local intensity variations of the O 1s and the Ni 2p signal display an anticorrelated behavior. The coincidence of a high oxygen signal with a low Ni 2p intensity, which seemingly contradicts the chemical attraction between O and Ni, has been explained with a phase separation of the oxygen covered Rh(111)/Ni surface into a 3D-Ni oxide and into a Ni poor metallic phase. Macroscopic NiO islands (≈1 μm size) formed under reaction conditions have been identified as 2D-Ni oxide. Titration experiments of the oxygen covered Rh(111)/Ni surface with H2 demonstrated that the reactivity of oxygen is decreased by an order of magnitude through the addition of 0.6 ML Ni. An excitation mechanism is proposed in which the periodic formation and reduction of NiO modulate the catalytic activity.

Visible light alters yeast metabolic rhythms by inhibiting respiration.

PubMed

Robertson, James Brian; Davis, Chris R; Johnson, Carl Hirschie

2013-12-24

Exposure of cells to visible light in nature or in fluorescence microscopy often is considered to be relatively innocuous. However, using the yeast respiratory oscillation (YRO) as a sensitive measurement of metabolism, we find that non-UV visible light has a significant impact on yeast metabolism. Blue/green wavelengths of visible light shorten the period and dampen the amplitude of the YRO, which is an ultradian rhythm of cell metabolism and transcription. The wavelengths of light that have the greatest effect coincide with the peak absorption regions of cytochromes. Moreover, treating yeast with the electron transport inhibitor sodium azide has similar effects on the YRO as visible light. Because impairment of respiration by light would change several state variables believed to play vital roles in the YRO (e.g., oxygen tension and ATP levels), we tested oxygen's role in YRO stability and found that externally induced oxygen depletion can reset the phase of the oscillation, demonstrating that respiratory capacity plays a role in the oscillation's period and phase. Light-induced damage to the cytochromes also produces reactive oxygen species that up-regulate the oxidative stress response gene TRX2 that is involved in pathways that enable sustained growth in bright visible light. Therefore, visible light can modulate cellular rhythmicity and metabolism through unexpectedly photosensitive pathways.

Low levels of lipopolysaccharide modulate mitochondrial oxygen consumption in skeletal muscle

PubMed Central

Frisard, Madlyn I.; Wu, Yaru; McMillan, Ryan P.; Voelker, Kevin A.; Wahlberg, Kristin A.; Anderson, Angela S.; Boutagy, Nabil; Resendes, Kyle; Ravussin, Eric; Hulver, Matthew W.

2014-01-01

Objective We have previously demonstrated that activation of toll-like receptor 4 (TLR4) in skeletal muscle results in an increased reliance on glucose as an energy source and a concomitant decrease in fatty acid oxidation under basal conditions. Herein, we examined the effects of lipopolysaccharide (LPS), the primary ligand for TLR4, on mitochondrial oxygen consumption in skeletal muscle cell culture and isolated mitochondria. Materials/ methods Skeletal muscle cell cultures were exposed to LPS and oxygen consumption was assessed using a Seahorse Bioscience extracellular flux analyzer. Mice were also exposed to LPS and oxygen consumption was assessed in mitochondria isolated from skeletal muscle. Results Acute LPS exposure resulted in significant reductions in cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP)-stimulated maximal respiration (state 3u) and increased oligomycin induced state 4 (state 4O) respiration in C2C12 and human primary myotubes. These findings were observed in conjunction with increased mRNA of uncoupling protein 3 (UCP3), superoxide dismutase 2 (SOD2), and pyruvate dehydrogenase activity. The LPS-mediated changes in substrate oxidation and maximal mitochondrial respiration were prevented in the presence of the antioxidants N-acetylcysteine and catalase, suggesting a potential role of reactive oxygen species in mediating these effects. Mitochondria isolated from red gastrocnemius and quadriceps femoris muscle from mice injected with LPS also demonstrated reduced respiratory control ratio (RCR), and ADP- and FCCP-stimulated respiration. Conclusion LPS exposure in skeletal muscle alters mitochondrial oxygen consumption and substrate preference, which is absent when antioxidants are present. PMID:25528444

REACTIVE OXYGEN SPECIES IN WHOLE BLOOD, BLOOD PLASMA AND BREAST MILK: VALIDATION OF A POTENTIAL MARKER OF EXPOSURE AND EFFECT

EPA Science Inventory

Reactive oxygen species (ROS) are recognized to contribute to the pathobiology of many diseases. We have applied a simple chemiluminescent (CL) probe to detect ROS in various biological fluids (plasma, whole blood, urine and breast milk) in an environmental arsenic drinking wate...

Herbivore derived fatty acid-amides elicit reactive oxygen species burst in plants

USDA-ARS?s Scientific Manuscript database

The formation of a reactive oxygen species (ROS) burst is a central response of plants to many forms of stress including pathogen attack, several abiotic stresses, damage and insect infestation. These ROS act as a direct defense as well as signaling and regulatory molecules. Perception of microbe or...

Formation and Detoxification of Reactive Oxygen Species

ERIC Educational Resources Information Center

Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

2004-01-01

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

Size-dependent cytotoxicity of yttrium oxide nanoparticles on primary osteoblasts in vitro

NASA Astrophysics Data System (ADS)

Zhou, Guoqiang; Li, Yunfei; Ma, Yanyan; Liu, Zhu; Cao, Lili; Wang, Da; Liu, Sudan; Xu, Wenshi; Wang, Wenying

2016-05-01

Yttrium oxide nanoparticles are an excellent host material for the rare earth metals and have high luminescence efficiency providing a potential application in photodynamic therapy and biological imaging. In this study, the effects of yttrium oxide nanoparticles with four different sizes were investigated using primary osteoblasts in vitro. The results demonstrated that the cytotoxicity generated by yttrium oxide nanoparticles depended on the particle size, and smaller particles possessed higher toxicological effects. For the purpose to elucidate the relationship between reactive oxygen species generation and cell damage, cytomembrane integrity, intracellular reactive oxygen species level, mitochondrial membrane potential, cell apoptosis rate, and activity of caspase-3 in cells were then measured. Increased reactive oxygen species level was also observed in a size-dependent way. Thus, our data demonstrated that exposure to yttrium oxide nanoparticles resulted in a size-dependent cytotoxicity in cultured primary osteoblasts, and reactive oxygen species generation should be one possible damage pathway for the toxicological effects produced by yttrium oxide particles. The results may provide useful information for more rational applications of yttrium oxide nanoparticles in the future.

Reactive Pendant Mn═O in a Synthetic Structural Model of a Proposed S4 State in the Photosynthetic Oxygen Evolving Complex.

PubMed

Vaddypally, Shivaiah; Kondaveeti, Sandeep K; Karki, Santosh; Van Vliet, Megan M; Levis, Robert J; Zdilla, Michael J

2017-04-05

The molecular mechanism of the Oxygen Evolving Center of photosystem II has been under debate for decades. One frequently cited proposal is the nucleophilic attack by water hydroxide on a pendant Mn═O moiety, though no chemical example of this reactivity at a manganese cubane cluster has been reported. We describe here the preparation, characterization, and a reactivity study of a synthetic manganese cubane cluster with a pendant manganese-oxo moiety. Reaction of this cluster with alkenes results in oxygen and hydrogen atom transfer reactions to form alcohol- and ketone-based oxygen-containing products. Nitrene transfer from core imides is negligible. The inorganic product is a cluster identical to the precursor, but with the pendant Mn═O moiety replaced by a hydrogen abstracted from the organic substrate, and is isolated in quantitative yield. 18 O and 2 H isotopic labeling studies confirm the transfer of atoms between the cluster and the organic substrate. The results suggest that the core cubane structure of this model compound remains intact, and that the pendant Mn═O moiety is preferentially reactive.

Melt containment member

DOEpatents

Rieken, Joel R.; Heidloff, Andrew J.

2014-09-09

A tubular melt containment member for transient containment of molten metals and alloys, especially reactive metals and alloys, includes a melt-contacting layer or region that comprises an oxygen-deficient rare earth oxide material that is less reactive as compared to the counterpart stoichiometric rare earth oxide. The oxygen-deficient (sub-stoichiometric) rare earth oxide can comprise oxygen-deficient yttria represented by Y.sub.2O.sub.3-x wherein x is from 0.01 to 0.1. Use of the oxygen-deficient rare earth oxide as the melt-contacting layer or region material reduces reaction with the melt for a given melt temperature and melt contact time.

Epic Immune Battles of History: Neutrophils vs. Staphylococcus aureus.

PubMed

Guerra, Fermin E; Borgogna, Timothy R; Patel, Delisha M; Sward, Eli W; Voyich, Jovanka M

2017-01-01

Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages. Staphylococcus aureus ( S. aureus ) is a prevalent Gram-positive bacterium that is a common commensal and causes a wide range of diseases from skin infections to endocarditis. Since its discovery, S. aureus has been a formidable neutrophil foe that has challenged the efficacy of this professional assassin. Indeed, proper clearance of S. aureus by neutrophils is essential to positive infection outcome, and S. aureus has developed mechanisms to evade neutrophil killing. Herein, we will review mechanisms used by S. aureus to modulate and evade neutrophil bactericidal mechanisms including priming, activation, chemotaxis, production of reactive oxygen species, and resolution of infection. We will also highlight how S. aureus uses sensory/regulatory systems to tailor production of virulence factors specifically to the triggering signal, e.g., neutrophils and defensins. To conclude, we will provide an overview of therapeutic approaches that may potentially enhance neutrophil antimicrobial functions.

Spermine reduces reactive oxygen species levels and decreases cryocapacitation in canine sperm cryopreservation.

PubMed

Setyawan, Erif Maha Nugraha; Kim, Min Jung; Oh, Hyun Ju; Kim, Geon A; Jo, Young Kwang; Lee, Seok Hee; Choi, Yoo Bin; Lee, Byeong Chun

2016-10-28

The objective of this study was to determine the ability of spermine to act as an antioxidant in scavenging reactive oxygen species (ROS), maintaining sperm function and decreasing cryocapacitation after cryopreservation. Although motility did not increase with spermine treatment, values for membrane integrity were significantly increased (P < 0.05). Higher percentages of linearity and straightness with a lower amplitude of lateral head displacement (ALH) indicated that spermine inhibits hyperactivation. Concentrations of intracellular and extracellular ROS were decreased in the treatment group (P < 0.05). Higher expression of an anti-apoptotic gene (Bcl-2) and lower expression of a pro-apoptotic gene (Bax), together with decreased expression of the mitochondrial ROS modulator ROMO1, DNA repair due to oxidative damage (OGG1), spermine synthase (SMS), NADPH oxidase associated with motility (NOX5) and spermine amino oxidase (SMOX), all showed that 5.0 mM spermine treatment was beneficial to spermatozoa. Furthermore, the proportion of live spermatozoa with intact acrosomes after thawing in the treatment group was higher than in the control. After incubation in canine capacitating medium, numbers of live capacitated spermatozoa with reacted acrosomes were higher than in the control. Our results indicate that 5.0 mM spermine is an optimal concentration for maintaining sperm function, reducing ROS production, preventing apoptosis and adverse effects of cryocapacitation during canine sperm cryopreservation. Copyright © 2016 Elsevier Inc. All rights reserved.

Leishmania amazonensis fails to induce the release of reactive oxygen intermediates by CBA macrophages.

PubMed

Almeida, T F; Palma, L C; Mendez, L C; Noronha-Dutra, A A; Veras, P S T

2012-10-01

CBA mouse macrophages effectively control Leishmania major infection, yet are permissive to Leishmania amazonensis. It has been established that some Leishmania species are destroyed by reactive oxygen species (ROS). However, other species of Leishmania exhibit resistance to ROS or even down-modulate ROS production. We hypothesized that L. amazonensis-infected macrophages reduce ROS production soon after parasite-cell interaction. Employing a highly sensitive analysis technique based on chemiluminescence, the production of superoxide (O(·-)(2)) and hydrogen peroxide (H(2)O(2)) by L. major- or L. amazonensis-infected CBA macrophages were measured. L. major induces macrophages to release levels of (O(·-)(2)) 3·5 times higher than in uninfected cells. This (O(·-)(2)) production is partially dependent on NADPH oxidase (NOX) type 2. The level of accumulated H(2)O(2) is 20 times higher in L. major-than in L. amazonensis-infected cells. Furthermore, macrophages stimulated with L. amazonensis release amounts of ROS similar to uninfected cells. These findings support previous studies showing that CBA macrophages are effective in controlling L. major infection by a mechanism dependent on both (O(·-)(2)) production and H(2)O(2) generation. Furthermore, these data reinforce the notion that L. amazonensis survive inside CBA macrophages by reducing ROS production during the phagocytic process. © 2012 Blackwell Publishing Ltd.

Hexokinase II acts through UCP3 to suppress mitochondrial reactive oxygen species production and maintain aerobic respiration.

PubMed

Mailloux, Ryan J; Dumouchel, Tyler; Aguer, Céline; deKemp, Rob; Beanlands, Rob; Harper, Mary-Ellen

2011-07-15

UCP3 (uncoupling protein-3) mitigates mitochondrial ROS (reactive oxygen species) production, but the mechanisms are poorly understood. Previous studies have also examined UCP3 effects, including decreased ROS production, during metabolic states when fatty acid oxidation is high (e.g. a fasting state). However, the role of UCP3 when carbohydrate oxidation is high (e.g. fed state) has remained largely unexplored. In the present study, we show that mitochondrial-bound HK (hexokinase) II curtails oxidative stress and enhances aerobic metabolism of glucose in the fed state in a UCP3-dependent manner. Genetic knockout or inhibition of UCP3 significantly decreased mitochondrial-bound HKII. Furthermore, UCP3 was required for the HKII-mediated decrease in mitochondrial ROS emission. Intriguingly, the UCP3-mediated modulation of mitochondria-associated HKII was only observed in cells cultured under high-glucose conditions. UCP3 was required to maintain high rates of aerobic metabolism in high-glucose-treated cells and in muscle of fed mice. Deficiency in UCP3 resulted in a metabolic shift that favoured anaerobic glycolytic metabolism, increased glucose uptake and increased sensitivity to oxidative challenge. PET (positron emission tomography) of [18F]fluoro-deoxyglucose uptake confirmed these findings in UCP3-knockout and wild-type mice. Collectively, our findings link the anti-oxidative and metabolic functions of UCP3 through a surprising molecular connection with mitochondrial-bound HKII.

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system.

PubMed

Kietzmann, Thomas; Petry, Andreas; Shvetsova, Antonina; Gerhold, Joachim M; Görlach, Agnes

2017-06-01

Cardiovascular diseases are among the leading causes of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiologically elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape, which can affect DNA methylation, post-translational histone modifications, ATP-dependent alterations to chromatin and non-coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases. While it has long been accepted that epigenetic changes are imprinted during development or even inherited and are not changed after reaching the lineage-specific expression profile, it becomes more and more clear that epigenetic modifications are highly dynamic. Thus, they might provide an important link between the actions of ROS and cardiovascular diseases. This review will provide an overview of the role of ROS in modulating the epigenetic landscape in the context of the cardiovascular system. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. © 2017 The British Pharmacological Society.

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system

PubMed Central

Kietzmann, Thomas; Petry, Andreas; Shvetsova, Antonina; Gerhold, Joachim M

2017-01-01

Cardiovascular diseases are among the leading causes of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiologically elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape, which can affect DNA methylation, post‐translational histone modifications, ATP‐dependent alterations to chromatin and non‐coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases. While it has long been accepted that epigenetic changes are imprinted during development or even inherited and are not changed after reaching the lineage‐specific expression profile, it becomes more and more clear that epigenetic modifications are highly dynamic. Thus, they might provide an important link between the actions of ROS and cardiovascular diseases. This review will provide an overview of the role of ROS in modulating the epigenetic landscape in the context of the cardiovascular system. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:28332701

Conversion of Natively Unstructured α-Synuclein to Its α-Helical Conformation Significantly Attenuates Production of Reactive Oxygen Species

PubMed Central

Zhou, Binbin; Hao, Yuanqiang; Wang, Chengshan; Li, Ding; Liu, You-Nian; Zhou, Feimeng

2012-01-01

The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson’s disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV–visible spectroscopic experiments reveal that both Cu(I) and Cu(II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured α-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194–196), α-helical α-syn stabilizes Cu(I) by more than three orders of magnitude. Through the measurements of H2O2 and hydroxyl radicals (OH•) in solutions containing different forms of Cu(II) (free and complexed by unstructured or α-helical α-syn), we demonstrate that the significantly enhanced Cu(I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured α-syn to its α-helical conformation in vivo could significantly attenuate the copper-modulated ROS production. PMID:23123341

Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.

PubMed

Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

2018-03-20

Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p < 0.001) and disruption of insulin secretion ( p < 0.001) associated with of reactive oxygen species (ROS) production and a modulation of pro-oxidant and antioxidant signaling pathway. Cell pre-treatments with extracts considerably increased cell viability (+86% p < 0.001) for simmondsin and +74% ( p < 0.001) for aqueous extract and insulin secretion. The extracts also markedly decreased ROS (-69% ( p < 0.001) for simmondsin and -59% ( p < 0.001) for aqueous extract) and caspase-3 activation and improved antioxidant defense, inhibiting p22phox and increasing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) levels (+70%, p < 0.001) for aqueous extract. Simmondsin had no impact on Nrf2 levels. The richness and diversity of molecules present in jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

Peptidoglycan and lipoteichoic acid, components of the streptococcal cell wall, have marked and differential effects on adhesion molecule expression and the production of reactive oxygen species in human whole blood leukocytes.

PubMed

Saetre, T; Kähler, H; Foster, S J; Lyberg, T

2000-07-01

To elucidate the pathophysiology of infections with Streptococcus pyogenes we applied flow cytometric techniques to study dose-response and time-related effects of the streptococcal cell-wall-derived components lipoteichoic acid (LTA 0.005 to 50 microg/ml) and peptidoglycan (10 and 100 microg/ml) on the expression of leukocyte adhesion molecules, the CD14 receptor, and the production of leukocyte reactive oxygen species (ROS). LTA (50 microg/ml, 1-2 h) markedly increased the expression of CD11b (approximately 5-fold), CD11c (approximately 2-fold) and CD11a. Concomitantly, CD62L was downregulated (60%). Peptidoglycan alone or in combination with LTA had little effect on adhesion molecules, except for an amplification of the downregulation of CD62L to 90%. Monocyte CD14 expression was doubled by LTA. Leukocyte ROS production was 10-fold and 5-fold increased by peptidoglycan in granulocytes and monocytes, respectively. LTA alone had no effect, while the combination of peptidoglycan with LTA doubled the increase in ROS caused by peptidoglycan. LTA and peptidoglycan had marked and differential effects: LTA caused mainly adhesion molecule modulation, whereas peptidoglycan mainly increased ROS production. These changes are important in inflammatory cell activation and recruitment, intracellular microbial killing and adverse tissue injury.

Arabidopsis MLO2 is a negative regulator of sensitivity to extracellular reactive oxygen species.

PubMed

Cui, Fuqiang; Wu, Hongpo; Safronov, Omid; Zhang, Panpan; Kumar, Rajeev; Kollist, Hannes; Salojärvi, Jarkko; Panstruga, Ralph; Overmyer, Kirk

2018-04-01

The atmospheric pollutant ozone (O 3 ) is a strong oxidant that causes extracellular reactive oxygen species (ROS) formation, has significant ecological relevance, and is used here as a non-invasive ROS inducer to study plant signalling. Previous genetic screens identified several mutants exhibiting enhanced O 3 sensitivity, but few with enhanced tolerance. We found that loss-of-function mutants in Arabidopsis MLO2, a gene implicated in susceptibility to powdery mildew disease, exhibit enhanced dose-dependent tolerance to O 3 and extracellular ROS, but a normal response to intracellular ROS. This phenotype is increased in a mlo2 mlo6 mlo12 triple mutant, reminiscent of the genetic redundancy of MLO genes in powdery mildew resistance. Stomatal assays revealed that enhanced O 3 tolerance in mlo2 mutants is not caused by altered stomatal conductance. We explored modulation of the mlo2-associated O 3 tolerance, powdery mildew resistance, and early senescence phenotypes by genetic epistasis analysis, involving mutants with known effects on ROS sensitivity or antifungal defence. Mining of publicly accessible microarray data suggests that these MLO proteins regulate accumulation of abiotic stress response transcripts, and transcript accumulation of MLO2 itself is O 3 responsive. In summary, our data reveal MLO2 as a novel negative regulator in plant ROS responses, which links biotic and abiotic stress response pathways. © 2018 John Wiley & Sons Ltd.

The production of reactive oxygen species and the mitochondrial membrane potential are modulated during onion oil-induced cell cycle arrest and apoptosis in A549 cells.

PubMed

Wu, Xin-jiang; Stahl, Thorsten; Hu, Ying; Kassie, Fekadu; Mersch-Sundermann, Volker

2006-03-01

Protective effects of Allium vegetables against cancers have been shown extensively in experimental animals and epidemiologic studies. We investigated cell proliferation and the induction of apoptosis by onion oil extracted from Allium cepa, a widely consumed Allium vegetable, in human lung cancer A549 cells. GC/MS analysis suggested that propyl sulfides but not allyl sulfides are major sulfur-containing constituents of onion oil. Onion oil at 12.5 mg/L significantly induced apoptosis (13% increase of apoptotic cells) as indicated by sub-G1 DNA content. It also caused cell cycle arrest at the G2/M phase; 25 mg/L onion oil increased the percentage of G2/M cells almost 6-fold compared with the dimethyl sulfoxide control. The action of onion oil may occur via a reactive oxygen species-dependent pathway because cell cycle arrest and apoptosis were blocked by the antioxidants N-acetylcysteine and exogenous glutathione. Marked collapse of the mitochondrial membrane potential suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by onion oil. Expression of phospho-cdc2 and phospho-cyclin B1 were downregulated by onion oil, perhaps accounting for the G2/M arrest. Overall, these results suggest that onion oil may exert chemopreventive action by inducing cell cycle arrest and apoptosis in tumor cells.

A benzoxazine derivative induces vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 by elevating NADPH oxidase activity and reactive oxygen species levels.

PubMed

Zhao, Jing; He, Qiuxia; Cheng, Yizhe; Zhao, Baoxiang; Zhang, Yun; Zhang, Shangli; Miao, Junying

2009-09-01

Previously, we found that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO) promoted apoptosis of human umbilical vascular endothelial cells (HUVECs) deprived of growth factors. In this study, we aimed to investigate the effect of DBO and its mechanism of action on angiogenesis and apoptosis of HUVECs in the presence of fibroblast growth factor-2 (FGF-2), which promotes angiogenesis and inhibits apoptosis in vivo and in vitro. DBO significantly inhibited capillary-like tube formation by promoting apoptosis of HUVECs in the presence of FGF-2 in vitro. Furthermore, DBO elevated the levels of reactive oxygen species (ROS) and nitric oxide (NO) and increased the activity of NADPH oxidase and inducible nitric oxide synthase (iNOS) in promoting apoptosis under this condition. Moreover, when NADPH oxidase was inhibited by its specific inhibitor, dibenziodolium chloride (DPI), DBO could not elevate ROS and NO levels in HUVECs. The data suggest that DBO is a new modulator of apoptosis in vitro, and it might function by increasing the activity of NADPH oxidase and iNOS, subsequently elevating the levels of ROS and NO in HUVECs. The findings of this study provide a new small molecule for investigating the FGF-2/NADPH oxidase/iNOS signaling pathway in apoptosis.

Epic Immune Battles of History: Neutrophils vs. Staphylococcus aureus

PubMed Central

Guerra, Fermin E.; Borgogna, Timothy R.; Patel, Delisha M.; Sward, Eli W.; Voyich, Jovanka M.

2017-01-01

Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages. Staphylococcus aureus (S. aureus) is a prevalent Gram-positive bacterium that is a common commensal and causes a wide range of diseases from skin infections to endocarditis. Since its discovery, S. aureus has been a formidable neutrophil foe that has challenged the efficacy of this professional assassin. Indeed, proper clearance of S. aureus by neutrophils is essential to positive infection outcome, and S. aureus has developed mechanisms to evade neutrophil killing. Herein, we will review mechanisms used by S. aureus to modulate and evade neutrophil bactericidal mechanisms including priming, activation, chemotaxis, production of reactive oxygen species, and resolution of infection. We will also highlight how S. aureus uses sensory/regulatory systems to tailor production of virulence factors specifically to the triggering signal, e.g., neutrophils and defensins. To conclude, we will provide an overview of therapeutic approaches that may potentially enhance neutrophil antimicrobial functions. PMID:28713774

Effects of cyanobacterial toxins and cyanobacterial cell-free crude extract on germination of alfalfa (Medicago sativa) and induction of oxidative stress.

PubMed

Pflugmacher, Stephan; Jung, Katharina; Lundvall, Linn; Neumann, Stefanie; Peuthert, Anja

2006-09-01

Cyanobacterial toxins have adverse effects on both terrestrial and aquatic plants. Microcystins are cyclic heptapeptides and an important group of cyanotoxins. When lake water contaminated with cyanobacterial blooms is used for spray irrigation, these toxins can come in contact with agricultural plants. During the exposure to these toxins, reactive oxygen species can form. These reactive oxygen species have a strong reactivity and are able to interact with other cellular compounds (lipids, protein, and DNA). Plants have antioxidative systems that will limit the negative effects caused by reactive oxygen species. These systems consist of enzymes, such as superoxide dismutase, catalase, and ascorbate peroxidase, and nonenzymatic substances, such as reduced glutathione or vitamins. The aim of the present study was to investigate the effects of cyanobacterial toxins (microcystins and anatoxin-a) and cyanobacterial cell-free crude extract on alfalfa (Medicago sativa) seedlings. Inhibition of germination and root growth was observed with toxin concentrations of 5.0 microg/L. Also, oxidative damage, such as lipid peroxidation, was detected after the exposure of alfalfa seedlings to the toxin. Reactive oxygen detoxifying enzymes were elevated, showing a marked response in alfalfa to oxidative stress caused by the exposure to cyanobacterial metabolites that might influence the growth and development of these plants negatively.

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines.

PubMed

Dashdorj, Amarjargal; Jyothi, K R; Lim, Sangbin; Jo, Ara; Nguyen, Minh Nam; Ha, Joohun; Yoon, Kyung-Sik; Kim, Hyo Jong; Park, Jae-Hoon; Murphy, Michael P; Kim, Sung Soo

2013-08-06

MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation. Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed. Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells. Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines

PubMed Central

2013-01-01

Background MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation. Methods Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed. Results Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells. Conclusion Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease. PMID:23915129

Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes.

PubMed

Mokarizadeh, Aram; Delirezh, Nowruz; Morshedi, Ahhmad; Mosayebi, Ghasem; Farshid, Amir-Abbas; Dalir-Naghadeh, Bahram

2012-01-01

Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes' membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.

Developing Master Keys to Brain Pathology, Cancer and Aging from the Structural Biology of Proteins Controlling Reactive Oxygen Species and DNA Repair

PubMed Central

Perry, J. Jefferson P.; Fan, Li; Tainer, John A.

2007-01-01

This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to varying extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression. PMID:17174478

Production and removal of superoxide anion radical by artificial metalloenzymes and redox-active metals

PubMed Central

Kawano, Tomonori; Kagenishi, Tomoko; Kadono, Takashi; Bouteau, François; Hiramatsu, Takuya; Lin, Cun; Tanaka, Kenichiro; Tanaka, Licca; Mancuso, Stefano; Uezu, Kazuya; Okobira, Tadashi; Furukawa, Hiroka; Iwase, Junichiro; Inokuchi, Reina; Baluška, Frantisek; Yokawa, Ken

2015-01-01

Generation of reactive oxygen species is useful for various medical, engineering and agricultural purposes. These include clinical modulation of immunological mechanism, enhanced degradation of organic compounds released to the environments, removal of microorganisms for the hygienic purpose, and agricultural pest control; both directly acting against pathogenic microorganisms and indirectly via stimulation of plant defense mechanism represented by systemic acquired resistance and hypersensitive response. By aiming to develop a novel classes of artificial redox-active biocatalysts involved in production and/or removal of superoxide anion radicals, recent attempts for understanding and modification of natural catalytic proteins and functional DNA sequences of mammalian and plant origins are covered in this review article. PMID:27066179

The Reactive Species Interactome: Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

PubMed Central

Koning, Anne; Kuhnle, Gunter G.C.; Nagy, Peter; Bianco, Christopher L.; Pasch, Andreas; Wink, David A.; Fukuto, Jon M.; Jackson, Alan A.; van Goor, Harry; Olson, Kenneth R.

2017-01-01

Abstract Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level. Critical Issues: To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses. Future Directions: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 27, 684–712. PMID:28398072

Singlet oxygen generation as a major cause for parasitic reactions during cycling of aprotic lithium-oxygen batteries

NASA Astrophysics Data System (ADS)

Mahne, Nika; Schafzahl, Bettina; Leypold, Christian; Leypold, Mario; Grumm, Sandra; Leitgeb, Anita; Strohmeier, Gernot A.; Wilkening, Martin; Fontaine, Olivier; Kramer, Denis; Slugovc, Christian; Borisov, Sergey M.; Freunberger, Stefan A.

2017-03-01

Non-aqueous metal-oxygen batteries depend critically on the reversible formation/decomposition of metal oxides on cycling. Irreversible parasitic reactions cause poor rechargeability, efficiency, and cycle life, and have predominantly been ascribed to the reactivity of reduced oxygen species with cell components. These species, however, cannot fully explain the side reactions. Here we show that singlet oxygen forms at the cathode of a lithium-oxygen cell during discharge and from the onset of charge, and accounts for the majority of parasitic reaction products. The amount increases during discharge, early stages of charge, and charging at higher voltages, and is enhanced by the presence of trace water. Superoxide and peroxide appear to be involved in singlet oxygen generation. Singlet oxygen traps and quenchers can reduce parasitic reactions effectively. Awareness of the highly reactive singlet oxygen in non-aqueous metal-oxygen batteries gives a rationale for future research towards achieving highly reversible cell operation.

Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer.

PubMed

Choe, Cholho; Yang, Ling; Lv, Zhanao; Mo, Wanling; Chen, Zhuqi; Li, Guangxin; Yin, Guochuan

2015-05-21

Redox-inactive metal ions can modulate the reactivity of redox-active metal ions in a variety of biological and chemical oxidations. Many synthetic models have been developed to help address the elusive roles of these redox-inactive metal ions. Using a non-heme manganese(II) complex as the model, the influence of redox-inactive metal ions as a Lewis acid on its catalytic efficiency in oxygen atom transfer was investigated. In the absence of redox-inactive metal ions, the manganese(II) catalyst is very sluggish, for example, in cyclooctene epoxidation, providing only 9.9% conversion with 4.1% yield of epoxide. However, addition of 2 equiv. of Al(3+) to the manganese(II) catalyst sharply improves the epoxidation, providing up to 97.8% conversion with 91.4% yield of epoxide. EPR studies of the manganese(II) catalyst in the presence of an oxidant reveal a 16-line hyperfine structure centered at g = 2.0, clearly indicating the formation of a mixed valent di-μ-oxo-bridged diamond core, Mn(III)-(μ-O)2-Mn(IV). The presence of a Lewis acid like Al(3+) causes the dissociation of this diamond Mn(III)-(μ-O)2-Mn(IV) core to form monomeric manganese(iv) species which is responsible for improved epoxidation efficiency. This promotional effect has also been observed in other manganese complexes bearing various non-heme ligands. The findings presented here have provided a promising strategy to explore the catalytic reactivity of some di-μ-oxo-bridged complexes by adding non-redox metal ions to in situ dissociate those dimeric cores and may also provide clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate.

The origins of marine bioluminescence: turning oxygen defence mechanisms into deep-sea communication tools.

PubMed

Rees, J F; de Wergifosse, B; Noiset, O; Dubuisson, M; Janssens, B; Thompson, E M

1998-04-01

Bioluminescence, the emission of ecologically functional light by living organisms, emerged independently on several occasions, yet the evolutionary origins of most bioluminescent systems remain obscure. We propose that the luminescent substrates of the luminous reactions (luciferins) are the evolutionary core of most systems, while luciferases, the enzymes catalysing the photogenic oxidation of the luciferin, serve to optimise the expression of the endogenous chemiluminescent properties of the luciferin. Coelenterazine, a luciferin occurring in many marine bioluminescent groups, has strong antioxidative properties as it is highly reactive with reactive oxygen species such as the superoxide anion or peroxides. We suggest that the primary function of coelenterazine was originally the detoxification of the deleterious oxygen derivatives. The functional shift from its antioxidative to its light-emitting function might have occurred when the strength of selection for antioxidative defence mechanisms decreased. This might have been made possible when marine organisms began colonising deeper layers of the oceans, where exposure to oxidative stress is considerably reduced because of reduced light irradiance and lower oxygen levels. A reduction in metabolic activity with increasing depth would also have decreased the endogenous production of reactive oxygen species. Therefore, in these organisms, mechanisms for harnessing the chemiluminescence of coelenterazine in specialised organs could have developed, while the beneficial antioxidative properties were maintained in other tissues. The full range of graded irradiance in the mesopelagic zone, where the majority of organisms are bioluminescent, would have provided a continuum for the selection and improvement of proto-bioluminescence. Although the requirement for oxygen or reactive oxygen species observed in bioluminescent systems reflects the high energy required to produce visible light, it may suggest that oxygen-detoxifying mechanisms provided excellent foundations for the emergence of many bioluminescent systems.

Exogenous acetaldehyde as a tool for modulating wine color and astringency during fermentation.

PubMed

Sheridan, Marlena K; Elias, Ryan J

2015-06-15

Wine tannins undergo modifications during fermentation and storage that can decrease their perceived astringency and increase color stability. Acetaldehyde acts as a bridging compound to form modified tannins and polymeric pigments that are less likely to form tannin-protein complexes than unmodified tannins. Red wines are often treated with oxygen in order to yield acetaldehyde, however this approach can lead to unintended consequences due to the generation of reactive oxygen species. The present study employs exogenous acetaldehyde at relatively low and high treatment concentrations during fermentation to encourage tannin modification without promoting potentially deleterious oxidation reactions. The high acetaldehyde treatment significantly increased polymeric pigments in the wine without increasing concentrations of free and sulfite-bound acetaldehyde. Protein-tannin precipitation was also significantly decreased with the addition of exogenous acetaldehyde. These results indicate a possible treatment of wines early in their production to increase color stability and lower astringency of finished wines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesis.

PubMed

Pacl, Hayden T; Reddy, Vineel P; Saini, Vikram; Chinta, Krishna C; Steyn, Adrie J C

2018-07-01

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, encounters variable and hostile environments within the host. A major component of these hostile conditions is reductive and oxidative stresses induced by factors modified by the host immune response, such as oxygen tension, NO or CO gases, reactive oxygen and nitrogen intermediates, the availability of different carbon sources and changes in pH. It is therefore essential for Mtb to continuously monitor and appropriately respond to the microenvironment. To this end, Mtb has developed various redox-sensitive systems capable of monitoring its intracellular redox environment and coordinating a response essential for virulence. Various aspects of Mtb physiology are regulated by these systems, including drug susceptibility, secretion systems, energy metabolism and dormancy. While great progress has been made in understanding the mechanisms and pathways that govern the response of Mtb to the host's redox environment, many questions in this area remain unanswered. The answers to these questions are promising avenues for addressing the tuberculosis crisis.

Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase.

PubMed

Berisha, H; Foda, H; Sakakibara, H; Trotz, M; Pakbaz, H; Said, S I

1990-08-01

Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.

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

PubMed

McMonnies, Charles

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

Isotope exchange in oxide-containing catalyst

NASA Technical Reports Server (NTRS)

Brown, Kenneth G. (Inventor); Upchurch, Billy T. (Inventor); Hess, Robert V. (Inventor); Miller, Irvin M. (Inventor); Schryer, David R. (Inventor); Sidney, Barry D. (Inventor); Wood, George M. (Inventor); Hoyt, Ronald F. (Inventor)

1989-01-01

A method of exchanging rare-isotope oxygen for common-isotope oxygen in the top several layers of an oxide-containing catalyst is disclosed. A sample of an oxide-containing catalyst is exposed to a flowing stream of reducing gas in an inert carrier gas at a temperature suitable for the removal of the reactive common-isotope oxygen atoms from the surface layer or layers of the catalyst without damaging the catalyst structure. The reduction temperature must be higher than any at which the catalyst will subsequently operate. Sufficient reducing gas is used to allow removal of all the reactive common-isotope oxygen atoms in the top several layers of the catalyst. The catalyst is then reoxidized with the desired rare-isotope oxygen in sufficient quantity to replace all of the common-isotope oxygen that was removed.

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

Treesearch

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

2009-01-01

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

Laccase and its role in production of extracellular reactive oxygen species during wood decay by the brown rot basidiomycete Postia placenta

Treesearch

Dongsheng Wei; Carl J. Houtman; Alexander N. Kapich; Christopher G. Hunt; Daniel Cullen; Kenneth E. Hammel

2010-01-01

Brown rot basidiomycetes initiate wood decay by producing extracellular reactive oxygen species that depolymerize the structural polysaccharides of lignocellulose. Secreted fungal hydroquinones are considered one contributor because they have been shown to reduce Fe3+, thus generating perhydroxyl radicals and Fe2+, which...

Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

USDA-ARS?s Scientific Manuscript database

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...

Induction of molecular endpoints by reactive oxygen species in human lung cells predicted by physical chemical properties of engineered nanoparticles

EPA Science Inventory

A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), and various types of DNA and protein damage in human respiratory BEAS-2B cells exposed in vitro for 72 hours at se...

Proteomic analysis of UVB-induced protein expression- and redox-dependent changes in skin fibroblasts using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis.

PubMed

Wu, Chieh-Lin; Chou, Hsiu-Chuan; Cheng, Chao-Sheng; Li, Ji-Min; Lin, Szu-Ting; Chen, Yi-Wen; Chan, Hong-Lin

2012-04-03

UVB is the most energetic and DNA-damaging to humans in ultraviolet radiation. Previous research has suggested that exposure to UVB causes skin pathologies because of direct DNA damage and the generation of reactive oxygen species (ROS). However, the detailed molecular mechanisms by which UVB leads to skin cancer have yet to be clarified. In the current study, normal skin fibroblast cells (CCD-966SK) were exposed to various doses of UVB, and the changes in protein expression and thiol reactivity were monitored with lysine- and cysteine-labeling 2D-DIGE and MALDI-TOF mass spectrometry. Our proteomic analysis revealed that 89 identified proteins showed significant changes in protein expression, and 37 in thiol reactivity. Many proteins that are known to be involved in protein folding, redox regulation and nucleotide biosynthesis were up-regulated under UVB irradiation. In contrast, proteins responsible for biosynthesis and protein degradation were down-regulated. In addition, the thiol-reactivity of proteins involving cytoskeleton, metabolism, and signal transduction were altered by UVB. In summary, these UVB-modulated cellular proteins and redox-regulated proteins might play important roles in the early stages of skin cancer formation and photoaging induced by UVB-irradiation. Such proteins might provide a potential target for the rational design of drugs to prevent UVB-induced diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of water turbidity and different temperatures on oxidative stress in caddisfly (Stenopsyche marmorata) larvae.

PubMed

Suzuki, Jumpei; Imamura, Masahiro; Nakano, Daisuke; Yamamoto, Ryosuke; Fujita, Masafumi

2018-07-15

Anthropogenic water turbidity derived from suspended solids (SS) is caused by reservoir sediment management practices such as drawdown flushing. Turbid water induces stress in many aquatic organisms, but the effects of turbidity on oxidative stress responses in aquatic insects have not yet been demonstrated. Here, we examined antioxidant responses, oxidative damage, and energy reserves in caddisfly (Stenopsyche marmorata) larvae exposed to turbid water (0 mg SS L -1 , 500 mg SS L -1 , and 2000 mg SS L -1 ) at different temperatures. We evaluated the combined effects of turbid water and temperature by measuring oxidative stress and using metabolic biomarkers. No turbidity level was significantly lethal to S. marmorata larvae. Moreover, there were no significant differences in antioxidant response or oxidative damage between the control and turbid water treatments at a low temperature (10 °C). However, at a high temperature (25 °C), turbid water modulated the activity of the antioxidant enzymes superoxide dismutase and catalase and the oxygen radical absorbance capacity as an indicator of the redox state of the insect larvae. Antioxidant defenses require energy, and high temperature was associated with low energy reserves, which might limit the capability of organisms to counteract reactive oxygen species. Moreover, co-exposure to turbid water and high temperature caused fluctuation of antioxidant defenses and increased the oxidative damage caused by the production of reactive oxygen species. Furthermore, the combined effect of high temperature and turbid water on antioxidant defenses and oxidative damage was larger than the individual effects. Therefore, our results demonstrate that exposure to both turbid water and high temperature generates additive and synergistic interactions causing oxidative stress in this aquatic insect species. Copyright © 2018. Published by Elsevier B.V.

Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giordano, Gennaro; Afsharinejad, Zhara; Guizzetti, Marina

2007-03-15

Over the past several years evidence has been accumulating from in vivo animal studies, observations in humans, and in vitro studies, that organophosphorus (OP) insecticides may induce oxidative stress. Such effects may contribute to some of the toxic manifestations of OPs, particularly upon chronic or developmental exposures. The aim of this study was to investigate the role of oxidative stress in the neurotoxicity of two commonly used OPs, chlorpyrifos (CPF) and diazinon (DZ), their oxygen analogs (CPO and DZO), and their 'inactive' metabolites (TCP and IMP), in neuronal cells from a genetic model of glutathione deficiency. Cerebellar granule neurons frommore » wild type mice (Gclm +/+) and mice lacking the modifier subunit of glutamate cysteine ligase (Gclm -/-), the first and limiting step in the synthesis of glutathione (GSH), were utilized. The latter display very low levels of GSH and are more susceptible to the toxicity of agents that increase oxidative stress. CPO and DZO were the most cytotoxic compounds, followed by CPF and DZ, while TCP and IMP displayed lower toxicity. Toxicity was significantly higher (10- to 25-fold) in neurons from Gclm (-/-) mice, and was antagonized by various antioxidants. Depletion of GSH from Gclm (+/+) neurons significantly increased their sensitivity to OP toxicity. OPs increased intracellular levels of reactive oxygen species and lipid peroxidation and in both cases the effects were greater in neurons from Gclm (-/-) mice. OPs did not alter intracellular levels of GSH, but significantly increased those of oxidized glutathione (GSSG). Cytotoxicity was not antagonized by cholinergic antagonists, but was decreased by the calcium chelator BAPTA-AM. These studies indicate that cytotoxicity of OPs involves generation of reactive oxygen species and is modulated by intracellular GSH, and suggest that it may involve disturbances in intracellular homeostasis of calcium.« less

Quantum mechanical calculations suggest that lytic polysaccharide monooxygenases use a copper-oxyl, oxygen-rebound mechanism

PubMed Central

Kim, Seonah; Ståhlberg, Jerry; Sandgren, Mats; Paton, Robert S.; Beckham, Gregg T.

2014-01-01

Lytic polysaccharide monooxygenases (LPMOs) exhibit a mononuclear copper-containing active site and use dioxygen and a reducing agent to oxidatively cleave glycosidic linkages in polysaccharides. LPMOs represent a unique paradigm in carbohydrate turnover and exhibit synergy with hydrolytic enzymes in biomass depolymerization. To date, several features of copper binding to LPMOs have been elucidated, but the identity of the reactive oxygen species and the key steps in the oxidative mechanism have not been elucidated. Here, density functional theory calculations are used with an enzyme active site model to identify the reactive oxygen species and compare two hypothesized reaction pathways in LPMOs for hydrogen abstraction and polysaccharide hydroxylation; namely, a mechanism that employs a η1-superoxo intermediate, which abstracts a substrate hydrogen and a hydroperoxo species is responsible for substrate hydroxylation, and a mechanism wherein a copper-oxyl radical abstracts a hydrogen and subsequently hydroxylates the substrate via an oxygen-rebound mechanism. The results predict that oxygen binds end-on (η1) to copper, and that a copper-oxyl–mediated, oxygen-rebound mechanism is energetically preferred. The N-terminal histidine methylation is also examined, which is thought to modify the structure and reactivity of the enzyme. Density functional theory calculations suggest that this posttranslational modification has only a minor effect on the LPMO active site structure or reactivity for the examined steps. Overall, this study suggests the steps in the LPMO mechanism for oxidative cleavage of glycosidic bonds. PMID:24344312

The importance of conceptual models in the reactive transport simulation of oxygen ingress in sparsely fractured crystalline rock.

PubMed

Macquarrie, K T B; Mayer, K U; Jin, B; Spiessl, S M

2010-03-01

Redox evolution in sparsely fractured crystalline rocks is a key, and largely unresolved, issue when assessing the geochemical suitability of deep geological repositories for nuclear waste. Redox zonation created by the influx of oxygenated waters has previously been simulated using reactive transport models that have incorporated a variety of processes, resulting in predictions for the depth of oxygen penetration that may vary greatly. An assessment and direct comparison of the various underlying conceptual models are therefore needed. In this work a reactive transport model that considers multiple processes in an integrated manner is used to investigate the ingress of oxygen for both single fracture and fracture zone scenarios. It is shown that the depth of dissolved oxygen migration is greatly influenced by the a priori assumptions that are made in the conceptual models. For example, the ability of oxygen to access and react with minerals in the rock matrix may be of paramount importance for single fracture conceptual models. For fracture zone systems, the abundance and reactivity of minerals within the fractures and thin matrix slabs between the fractures appear to provide key controls on O(2) attenuation. The findings point to the need for improved understanding of the coupling between the key transport-reaction feedbacks to determine which conceptual models are most suitable and to provide guidance for which parameters should be targeted in field and laboratory investigations. Copyright 2009 Elsevier B.V. All rights reserved.

Mechanisms of deep benzene oxidation on the Pt(1 1 1) surface using temperature-programmed reaction methods

NASA Astrophysics Data System (ADS)

Marsh, Anderson L.; Gland, John L.

2003-06-01

The catalytic oxidation of benzene on the Pt(1 1 1) surface has been characterized using temperature-programmed reaction spectroscopy (TPRS) over a wide range of benzene and oxygen coverages. Coadsorbed atomic oxygen and benzene are the primary reactants on the surface during the initial oxidation step. Benzene is oxidized over the 300-500 K range to produce carbon dioxide and water. Carbon-hydrogen and carbon-carbon bond activation are clearly rate-limiting steps for these reactions. Preferential oxidation causes depletion of bridge-bonded benzene, suggesting enhanced reactivity in this bonding configuration. When oxygen is in excess on the surface, all of the surface carbon and hydrogen is oxidized. When benzene is in excess on the surface, hydrogen produced by dehydrogenation is desorbed after all of the surface oxygen has been consumed. Repulsive interactions between benzene and molecular oxygen dominate at low temperatures. Preadsorption of oxygen inhibits adsorption of less reactive benzene in threefold hollow sites. The desorption temperature of this non-reactive chemisorbed benzene decreases and overlaps with the multilayer desorption peak with increasing oxygen exposure. The results presented here provide a clear picture of rate-limiting steps during deep oxidation of benzene on the Pt(1 1 1) surface.

Module Twelve: Series AC Resistive-Reactive Circuits; Basic Electricity and Electronics Individualized Learning System.

ERIC Educational Resources Information Center

Bureau of Naval Personnel, Washington, DC.

The module covers series circuits which contain both resistive and reactive components and methods of solving these circuits for current, voltage, impedance, and phase angle. The module is divided into six lessons: voltage and impedance in AC (alternating current) series circuits, vector computations, rectangular and polar notation, variational…

Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

PubMed

Guerra-Mora, J R; Perales-Caldera, E; Aguilar-León, D; Nava-Sanchez, C; Díaz-Cruz, A; Díaz-Martínez, N E; Santillán-Doherty, P; Torres-Villalobos, G; Bravo-Reyna, C C

Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury. Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured. Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group. Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model. Copyright © 2017 Elsevier Inc. All rights reserved.

Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species.

PubMed

Huang, Qiang; Shi, Jun; Gao, Bo; Zhang, Hong-Yang; Fan, Jing; Li, Xiao-Jie; Fan, Jin-Zhu; Han, Yue-Hu; Zhang, Jin-Kang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian

2015-04-01

Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata, is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Decreased photosynthetic rate under high temperature in wheat is due to lipid desaturation, oxidation, acylation, and damage of organelles.

PubMed

Djanaguiraman, M; Boyle, D L; Welti, R; Jagadish, S V K; Prasad, P V V

2018-04-05

High temperature is a major abiotic stress that limits wheat (Triticum aestivum L.) productivity. Variation in levels of a wide range of lipids, including stress-related molecular species, oxidative damage, cellular organization and ultrastructural changes were analyzed to provide an integrated view of the factors that underlie decreased photosynthetic rate under high temperature stress. Wheat plants of cultivar Chinese Spring were grown at optimum temperatures (25/15 °C, maximum/minimum) until the onset of the booting stage. Thereafter, plants were exposed to high temperature (35/25 °C) for 16 d. Compared with optimum temperature, a lower photosynthetic rate was observed at high temperature which is an interplay between thylakoid membrane damage, thylakoid membrane lipid composition, oxidative damage of cell organelle, and stomatal and non-stomatal limitations. Triacylglycerol levels were higher under high temperature stress. Polar lipid fatty acyl unsaturation was lower at high temperature, while triacylglycerol unsaturation was the same at high temperature and optimum temperature. The changes in lipid species indicates increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes under high temperature stress. Cumulative effect of high temperature stress led to generation of reactive oxygen species, cell organelle and membrane damage, and reduced antioxidant enzyme activity, and imbalance between reactive oxygen species and antioxidant defense system. Taken together with recent findings demonstrating that reactive oxygen species are formed from and are removed by thylakoid lipids, the data suggest that reactive oxygen species production, reactive oxygen species removal, and changes in lipid metabolism contribute to decreased photosynthetic rate under high temperature stress.

Potential Role of Carotenoids as Antioxidants in Human Health and Disease

PubMed Central

Fiedor, Joanna; Burda, Květoslava

2014-01-01

Carotenoids constitute a ubiquitous group of isoprenoid pigments. They are very efficient physical quenchers of singlet oxygen and scavengers of other reactive oxygen species. Carotenoids can also act as chemical quenchers undergoing irreversible oxygenation. The molecular mechanisms underlying these reactions are still not fully understood, especially in the context of the anti- and pro-oxidant activity of carotenoids, which, although not synthesized by humans and animals, are also present in their blood and tissues, contributing to a number of biochemical processes. The antioxidant potential of carotenoids is of particular significance to human health, due to the fact that losing antioxidant-reactive oxygen species balance results in “oxidative stress”, a critical factor of the pathogenic processes of various chronic disorders. Data coming from epidemiological studies and clinical trials strongly support the observation that adequate carotenoid supplementation may significantly reduce the risk of several disorders mediated by reactive oxygen species. Here, we would like to highlight the beneficial (protective) effects of dietary carotenoid intake in exemplary widespread modern civilization diseases, i.e., cancer, cardiovascular or photosensitivity disorders, in the context of carotenoids’ unique antioxidative properties. PMID:24473231

[Effect of low-energy 633 nm red light stimulation on proliferation and reactive oxygen species level of human epidermal cell line HaCaT].

PubMed

Chen, Z Y; Li, D L; Duan, X D; Peng, D Z

2016-09-20

To investigate the changes of proliferative activity and reactive oxygen species level of human epidermal cell line HaCaT after being irradiated with low-energy 633 nm red light. Irradiation distance was determined through preliminary experiment. HaCaT cells were conventionally sub-cultured with RPMI 1640 culture medium containing 10% fetal calf serum, 100 U/mL penicillin, and 100 μg/mL streptomycin. Cells of the third passage were used in the following experiments. (1) Cells were divided into blank control group and 0.082, 0.164, 0.245, 0.491, 1.472, 2.453, 4.910, and 9.810 J/cm(2) irradiation groups according to the random number table, with 3 wells in each group. Cells in blank control group were not irradiated, while cells in the latter 8 irradiation groups were irradiated with 633 nm red light for 10, 20, 30, 60, 180, 300, 600, and 1 200 s in turn. Cells were reirradiated once every 8 hours. After being irradiated for 48 hours (6 times) in irradiation groups, the proliferative activity of cells in 9 groups was determined with cell counting kit 8 and microplate reader (denoted as absorbance value). (2) Another batch of cells were grouped and irradiated as in experiment (1). After being irradiated for once in irradiation groups, cells in 9 groups were conventionally cultured for 60 min with detection reagent of reactive oxygen species. At post culture minute (PCM) 0 (immediately), 30, 60, and 120, reactive oxygen species level of cells was determined with microplate reader (denoted as absorbance value). (3) Another batch of cells were divided into blank control group, 0.082, 0.491, 2.453, and 9.810 J/cm(2) irradiation groups, and positive control group. Cells in blank control group and positive control group were not irradiated (positive control reagent of reactive oxygen species was added to cells in positive control group), and cells in irradiation groups were irradiated as in experiment (1) for once. The expression of reactive oxygen species in cells of each group was observed by confocal laser scanning microscope. Data were processed with one-way analysis of variance, analysis of variance for repeated measurement, and t test. (1) Irradiation distance was 10 cm. Proliferative activity of cells in blank control group and 0.082, 0.164, 0.245, 0.491, 1.472, 2.453, 4.910, and 9.810 J/cm(2) irradiation groups was 1.000, 1.116±0.031, 1.146±0.016, 1.162±0.041, 1.179±0.016, 1.207±0.016, 1.247±0.040, 1.097±0.059, and 0.951±0.118, respectively. Compared with that in blank control group, proliferative activity of cells in 0.082-2.453 J/cm(2) irradiation groups was significantly higher (with t values from -22.803 to -6.779, P values below 0.05). Proliferative activity of cells in 4.910 and 9.810 J/cm(2) irradiation groups was similar to that in blank control group (with t values respectively -2.854 and 0.711, P values above 0.05). (2) Compared with that in blank control group, reactive oxygen species level of cells was significantly enhanced at PCM 0 and 30 in 0.164-2.453 J/cm(2) irradiation groups (with t values from -12.453 to -4.684, P<0.05 or P<0.01), while that showed no significant change in 0.082, 4.910, and 9.810 J/cm(2) irradiation groups (with t values from -3.925 to -0.672, P values above 0.05). Compared with that in blank control group, reactive oxygen species level of cells was significantly enhanced at PCM 60 in 0.082-2.453 J/cm(2) irradiation groups (with t values from -11.387 to -4.717, P<0.05 or P<0.01). Compared with that in blank control group, reactive oxygen species level of cells was significantly enhanced at PCM 120 in 0.491-2.453 J/cm(2) irradiation groups (with t values from -10.657 to -6.644, P<0.05 or P<0.01). (3) Compared with that in blank control group, the expression of reactive oxygen species of cells was increased in 0.082, 0.491, and 2.453 J/cm(2) irradiation groups and positive control group. The expression of reactive oxygen species of cells in 9.810 J/cm(2) irradiation group was attenuated when compared with the expressions in the other irradiation groups. Reactive oxygen species expressed in mitochondria of cells in each group. Low-energy 633 nm red light can enhance the proliferation of human epidermal cell line HaCaT, and the effect is closely related to the increase of reactive oxygen species produced by mitochondria after being stimulated by red light irradiation.

The cotton WRKY transcription factor GhWRKY17 functions in drought and salt stress in transgenic Nicotiana benthamiana through ABA signaling and the modulation of reactive oxygen species production.

PubMed

Yan, Huiru; Jia, Haihong; Chen, Xiaobo; Hao, Lili; An, Hailong; Guo, Xingqi

2014-12-01

Drought and high salinity are two major environmental factors that significantly limit the productivity of agricultural crops worldwide. WRKY transcription factors play essential roles in the adaptation of plants to abiotic stresses. However, WRKY genes involved in drought and salt tolerance in cotton (Gossypium hirsutum) are largely unknown. Here, a group IId WRKY gene, GhWRKY17, was isolated and characterized. GhWRKY17 was found to be induced after exposure to drought, salt, H2O2 and ABA. The constitutive expression of GhWRKY17 in Nicotiana benthamiana remarkably reduced plant tolerance to drought and salt stress, as determined through physiological analyses of the germination rate, root growth, survival rate, leaf water loss and Chl content. GhWRKY17 transgenic plants were observed to be more sensitive to ABA-mediated seed germination and root growth. However, overexpressing GhWRKY17 in N. benthamiana impaired ABA-induced stomatal closure. Furthermore, we found that GhWRKY17 modulated the increased sensitivity of plants to drought by reducing the level of ABA, and transcript levels of ABA-inducible genes, including AREB, DREB, NCED, ERD and LEA, were clearly repressed under drought and salt stress conditions. Consistent with the accumulation of reactive oxygen species (ROS), reduced proline contents and enzyme activities, elevated electrolyte leakage and malondialdehyde, and lower expression of ROS-scavenging genes, including APX, CAT and SOD, the GhWRKY17 transgenic plants exhibited reduced tolerance to oxidative stress compared with wild-type plants. These results therefore indicate that GhWRKY17 responds to drought and salt stress through ABA signaling and the regulation of cellular ROS production in plants. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Apoptosis induction by silica nanoparticles mediated through reactive oxygen species in human liver cell line HepG2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmad, Javed; Ahamed, Maqusood, E-mail: maqusood@gmail.com; Akhtar, Mohd Javed

Silica nanoparticles are increasingly utilized in various applications including agriculture and medicine. In vivo studies have shown that liver is one of the primary target organ of silica nanoparticles. However, possible mechanisms of hepatotoxicity caused by silica nanoparticles still remain unclear. In this study, we explored the reactive oxygen species (ROS) mediated apoptosis induced by well-characterized 14 nm silica nanoparticles in human liver cell line HepG2. Silica nanoparticles (25–200 μg/ml) induced a dose-dependent cytotoxicity in HepG2 cells. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of ROS and lipid peroxidation and depletion ofmore » glutathione (GSH). Quantitative real-time PCR and immunoblotting results showed that both the mRNA and protein expressions of cell cycle checkpoint gene p53 and apoptotic genes (bax and caspase-3) were up-regulated while the anti-apoptotic gene bcl-2 was down-regulated in silica nanoparticles treated cells. Moreover, co-treatment of ROS scavenger vitamin C significantly attenuated the modulation of apoptotic markers along with the preservation of cell viability caused by silica nanoparticles. Our data demonstrated that silica nanoparticles induced apoptosis in human liver cells, which is ROS mediated and regulated through p53, bax/bcl-2 and caspase pathways. This study suggests that toxicity mechanisms of silica nanoparticles should be further investigated at in vivo level. -- Highlights: ► We explored the mechanisms of toxicity caused by silica NPs in human liver HepG2 cells. ► Silica NPs induced a dose-dependent cytotoxicity in HepG2 cells. ► Silica NPs induced ROS generation and oxidative stress in a dose-dependent manner. ► Silica NPs were also modulated apoptosis markers both at mRNA and protein levels. ► ROS mediated apoptosis induced by silica NPs was preserved by vitamin C.« less

Ethanol Influences on Bax Translocation, Mitochondrial Membrane Potential, and Reactive Oxygen Species Generation are Modulated by Vitamin E and Brain-Derived Neurotrophic Factor

PubMed Central

Heaton, Marieta Barrow; Paiva, Michael; Siler-Marsiglio, Kendra

2011-01-01

Background This study investigated ethanol influences on intracellular events which predispose developing neurons toward apoptosis, and the capacity of the antioxidant α-tocopherol (vitamin E) and the neurotrophin brain-derived neurotrophic factor (BDNF) to modulate these effects. Assessments were made of the following: (1) ethanol-induced translocation of the pro-apoptotic Bax protein to the mitochondrial membrane, a key upstream event in the initiation of apoptotic cell death; (2) disruption of the mitochondrial membrane potential (MMP) as a result of ethanol exposure, an important process in triggering the apoptotic cascade; and (3) generation of damaging reactive oxygen species (ROS) as a function of ethanol exposure. Methods These interactions were investigated in cultured postnatal day 8 neonatal rat cerebellar granule cells, a population vulnerable to developmental ethanol exposure in vivo and in vitro. Bax mitochondrial translocation was analyzed via subcellular fractionation followed by Western blot, and mitochondrial membrane integrity was determined using the lipophilic dye, JC-1, which exhibits potential-dependent accumulation in the mitochondrial membrane as a function of the MMP. Results Brief ethanol exposure in these preparations precipitated Bax translocation, but both vitamin E and BDNF reduced this effect to control levels. Ethanol treatment also resulted in a disturbance of the MMP, and this effect was blunted by the antioxidant and the neurotrophin. ROS generation was enhanced by a short ethanol exposure in these cells, but the production of these harmful free radicals was diminished to control levels by co-treatment with either vitamin E or BDNF. Conclusions These results indicate that both antioxidants and neurotrophic factors have the potential to ameliorate ethanol neurotoxicity, and suggest possible interventions which could be implemented in preventing or lessening the severity of the damaging effects of ethanol in the developing central nervous system seen in the fetal alcohol syndrome (FAS). PMID:21332533

Toluene Dose-Response and Preliminary Study of Proteomics for Neuronal Cell Lines

DTIC Science & Technology

2015-07-01

related to oxidative stress such as energy reserve metabolism, cell -death signaling, reactive oxygen species (ROS) defense, cytoskeletal rearrangement...protein nodes related to oxidative stress as characterized by gene ontologies for energy reserve metabolism, cell -death signaling, reactive oxygen ...process Myosin I complex myofibril assembly Cytoskeletal matrix assembly DNA methyltransferase Activity Cellular ketone Metabolic process Mesenchymal stem

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

USDA-ARS?s Scientific Manuscript database

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

Comparative In Vivo Effects of Hemoglobin-Based Oxygen Carriers (HBOC) with Varying Prooxidant and Physiological Reactivity.

PubMed

Toma, Vlad Al; Farcaș, Anca D; Roman, Ioana; Sevastre, Bogdan; Hathazi, Denisa; Scurtu, Florina; Damian, Grigore; Silaghi-Dumitrescu, Radu

2016-01-01

A series of hemoglobin-based oxygen carrier candidates (HBOC), previously noted for their differences in prooxidative and physiological reactivity, were compared in terms of the negative effects displayed upon injection in Wistar rats. At the concentrations tested, antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages.

Significant levels of extracellular reactive oxygen species produced by brown rot basidiomycetes on cellulose

Treesearch

Roni Cohen; Kenneth A. Jensen; Carl J. Houtman; Kenneth E. Hammel

2002-01-01

It is often proposed that brown rot basidiomycetes use extracellular reactive oxygen species (ROS) to accomplish the initial depolymerization of cellulose in wood, but little evidence has been presented to show that the fungi produce these oxidants in physiologically relevant quantities. We used [14C]phenethyl polyacrylate as a radical trap to estimate extracellular...

Effect of cefodizime and ceftriaxone on phagocytic function in patients with severe infections.

PubMed Central

Wenisch, C; Parschalk, B; Hasenhündl, M; Wiesinger, E; Graninger, W

1995-01-01

Thirty patients with severe bacterial infections were treated with 50 mg of cefodizime per kg of body weight once daily or 50 mg of ceftriaxone per kg once daily for 10 +/- 3 days. The effect of cefodizime and ceftriaxone on the phagocytic capacity and generation of reactive oxygen intermediates after phagocytosis by granulocytes was assessed prior to, during, and after therapy. Flow cytometry was used to study phagocytic capacity by measuring the uptake of fluorescein-labeled bacteria. The generation of reactive oxygen intermediates after phagocytosis was estimated by the quantification of the intracellular conversion of dihydrorhodamine 123 to rhodamine 123. Prior to therapy, patients in both groups exhibited a decreased capacity to phagocytize Escherichia coli and subsequently to generate reactive oxygen intermediates. Granulocyte function increased after the initiation of therapy and normalized within 7 days for the ceftriaxone-treated patients and within 3 days for the cefodizime group (P < 0.05). In the cefodizime group, an enhancement of phagocytic capacity was observed 14 days after the initiation of therapy (P < 0.05). Prior to therapy, phagocytic capacity was significantly correlated with the generation of reactive oxygen products (r = 0.674 and P < 0.005). PMID:7793871

Hydrogen peroxide generated by xanthine/xanthine oxidase system represses the proliferation of colorectal cancer cell line Caco-2.

PubMed

Sakuma, Satoru; Abe, Muneyuki; Kohda, Tetsuya; Fujimoto, Yohko

2015-01-01

The twin character of reactive oxygen species is substantiated by a growing body of evidence that reactive oxygen species within cells act as inducers and accelerators of the oncogenic phenotype of cancer cells, while reactive oxygen species can also induce cancer cell death and can therefore function as anti-tumorigenic species. The aim of this study was to assess a possible influence of xanthine/xanthine oxidase on the proliferation of colorectal cancer cell line Caco-2. xanthine/xanthine oxidase (2.5 µM/0.25 mU/ml-25 µM/2.5 mU/ml) dose-dependently inhibited the proliferation of Caco-2 cells. Experiments utilizing reactive oxygen species scavengers (superoxide dismutase, catalase and mannitol) and exogenous hydrogen peroxide revealed a major role of hydrogen peroxide in the xanthine/xanthine oxidase effect. Investigations utilizing annexin V-fluorescein/PI assay using flow cytometry, and the lactate dehydrogenase extracellular release assay indicated that hydrogen peroxide induced necrosis, but not apoptosis, in Caco-2 cells. These results suggest that hydrogen peroxide generated by xanthine/xanthine oxidase has the potential to suppress colorectal cancer cell proliferation.

Hexavalent chromium induces reactive oxygen species and impairs the antioxidant power of human erythrocytes and lymphocytes: Decreased metal reducing and free radical quenching ability of the cells.

PubMed

Husain, Nazim; Mahmood, Riaz

2017-08-01

The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to be closely associated with the generation of free radicals and reactive oxygen species. These species are produced when Cr(VI) is reduced to its trivalent form in the cell. This process results in oxidative stress due to an imbalance between the detoxifying ability of the cell and the production of free radicals. We have studied the effect of potassium dichromate (K 2 Cr 2 O 7 ), a [Cr(VI)] compound, on the antioxidant power of human erythrocytes and lymphocytes under in vitro conditions. Incubation of erythrocytes and lymphocytes with different concentrations of K 2 Cr 2 O 7 resulted in a marked dose-dependent decrease in reduced glutathione and an increase in oxidized glutathione and reactive oxygen species levels. The antioxidant power of the cells was decreased, as determined by metal reducing and free radical quenching assays. These results show that [Cr(VI)] upregulates the generation of reactive oxygen species and, as a consequence, the cellular antioxidant defences are compromised. The resulting oxidative stress may contribute to Cr(VI)-induced cellular damage.

Elementary surface processes during reactive magnetron sputtering of chromium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monje, Sascha; Corbella, Carles, E-mail: carles.corbella@rub.de; Keudell, Achim von

2015-10-07

The elementary surface processes occurring on chromium targets exposed to reactive plasmas have been mimicked in beam experiments by using quantified fluxes of Ar ions (400–800 eV) and oxygen atoms and molecules. For this, quartz crystal microbalances were previously coated with Cr thin films by means of high-power pulsed magnetron sputtering. The measured growth and etching rates were fitted by flux balance equations, which provided sputter yields of around 0.05 for the compound phase and a sticking coefficient of O{sub 2} of 0.38 on the bare Cr surface. Further fitted parameters were the oxygen implantation efficiency and the density of oxidationmore » sites at the surface. The increase in site density with a factor 4 at early phases of reactive sputtering is identified as a relevant mechanism of Cr oxidation. This ion-enhanced oxygen uptake can be attributed to Cr surface roughening and knock-on implantation of oxygen atoms deeper into the target. This work, besides providing fundamental data to control oxidation state of Cr targets, shows that the extended Berg's model constitutes a robust set of rate equations suitable to describe reactive magnetron sputtering of metals.« less

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

p53 as a retrovirus-induced oxidative stress modulator.

PubMed

Kim, Soo Jin; Wong, Paul K Y

2015-01-01

Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, ts1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that ts1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with ts1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator. © 2015 The Authors.

Protective Effects of Black Rice Extracts on Oxidative Stress Induced by tert-Butyl Hydroperoxide in HepG2 Cells

PubMed Central

Lee, Seon-Mi; Choi, Youngmin; Sung, Jeehye; Kim, Younghwa; Jeong, Heon-Sang; Lee, Junsoo

2014-01-01

Black rice contains many biologically active compounds. The aim of this study was to investigate the protective effects of black rice extracts (whole grain extract, WGE and rice bran extract, RBE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. Cellular reactive oxygen species (ROS), antioxidant enzyme activities, malondialdehyde (MDA) and glutathione (GSH) concentrations were evaluated as biomarkers of cellular oxidative status. Cells pretreated with 50 and 100 μg/mL of WGE or RBE were more resistant to oxidative stress in a dose-dependent manner. The highest WGE and BRE concentrations enhanced GSH concentrations and modulated antioxidant enzyme activities (glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase) compared to TBHP-treated cells. Cells treated with RBE showed higher protective effect compared to cells treated with WGE against oxidative insult. Black rice extracts attenuated oxidative insult by inhibiting cellular ROS and MDA increase and by modulating antioxidant enzyme activities in HepG2 cells. PMID:25580401

The role of redox mechanisms in hepatic chronic wound healing and fibrogenesis

PubMed Central

2012-01-01

Under physiological conditions, intracellular and tissue levels of reactive oxygen species (ROS) are carefully controlled and employed as fine modulators of signal transduction, gene expression and cell functional responses (redox signaling). A significant derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, plays a role in the pathogenesis of human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis, including chronic liver diseases. In this chapter major concepts and mechanisms in redox signaling will be briefly recalled to introduce a number of selected examples of redox-related mechanisms that can actively contribute to critical events in the natural history of a chronic liver diseases, including induction of cell death, perpetuation of chronic inflammatory responses and fibrogenesis. A major focus will be on redox-dependent mechanisms involved in the modulation of phenotypic responses of activated, myofibroblast-like, hepatic stellate cells (HSC/MFs), still considered as the most relevant pro-fibrogenic cells operating in chronic liver diseases. PMID:23259696

Endoplasmic Reticulum Stress Signaling in Mammalian Oocytes and Embryos: Life in the Balance

PubMed Central

Latham, Keith E.

2015-01-01

Mammalian oocytes and embryos are exquisitely sensitive to a wide range of insults related to physical stress, chemical exposure, and exposures to adverse maternal nutrition or health status. Although cells manifest specific responses to various stressors, many of these stressors intersect at the endoplasmic reticulum, where disruptions in protein folding and production of reactive oxygen species initiate downstream signaling events. These signals modulate mRNA translation and gene transcription, leading to recovery, activation of autophagy, or with severe and prolonged stress, apoptosis. ER stress signaling has recently come to the fore as a major contributor to embryo demise. Accordingly, agents that modulate or inhibit ER stress signaling have yielded beneficial effects on embryo survival and long-term developmental potential. We review here the mechanisms of ER stress signaling, their connections to mammalian oocytes and embryos, and the promising indications that interventions in this pathway may provide new opportunities for improving mammalian reproduction and health. PMID:25805126

SIRT3: Oncogene and Tumor Suppressor in Cancer

PubMed Central

Torrens-Mas, Margalida; Oliver, Jordi; Roca, Pilar; Sastre-Serra, Jorge

2017-01-01

Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in modulating oxygen reactive species (ROS) and limiting the oxidative damage in cellular components. SIRT3 targets different enzymes which regulate mitochondrial metabolism and participate in ROS detoxification, such as the complexes of the respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria homeostasis and has recently received great attention, as it is considered a fidelity protein for mitochondrial function. In some types of cancer, SIRT3 functions as a tumoral promoter, since it keeps ROS levels under a certain threshold compatible with cell viability and proliferation. On the contrary, other studies describe SIRT3 as a tumoral suppressor, as SIRT3 could trigger cell death under stress conditions. Thus, SIRT3 could have a dual role in cancer. In this regard, modulation of SIRT3 activity could be a new target to develop more personalized therapies against cancer. PMID:28704962

The Chemical Characteristics and Immune-Modulating Activity of Polysaccharides Isolated from Cold-Brew Coffee.

PubMed

Shin, Kwang-Soon

2017-06-01

To elucidate new biological ingredients in cold-brew coffee extracted with cold water, crude polysaccharide (CCP-0) was isolated by ethanol precipitation, and its immune-stimulating activities were assayed. CCP-0 mainly comprised galactose (53.6%), mannose (15.7%), arabinose (11.9%), and uronic acid (12.4%), suggesting that it might exist as a mixture of galactomannan and arabinogalactan. CCP-0 significantly increased cell proliferation on both murine peritoneal macrophages and splenocytes in a dose dependent manner. CCP-0 also significantly augmented nitric oxide and reactive oxygen species production by murine peritoneal macrophages. In addition, macrophages stimulated by CCP-0 enhanced production of various cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-12. In an in vitro assay for intestinal immune-modulating activity, CCP-0 showed higher bone-marrow cell-proliferation activity through Peyer's patch cells at 100 μg/mL than the negative control. These results suggest that CCP-0 may potentially enhance macrophage functions and the intestinal immune system.

Modulators of inhibitor of growth (ING) family expression in development and disease.

PubMed

Maher, Stacey K; Helbing, Caren C

2009-05-01

The inhibitor of growth (ING) gene family proteins regulate many critical cellular processes such as cell proliferation and growth, apoptosis, DNA repair, senescence, angiogenesis, and drug resistance. Their transcripts and proteins are differentially expressed in health and disease and there is evidence for developmental regulation. The vast majority of studies have characterized ING levels in the context of cancer. However, relatively little attention has been paid to the expression of ING family members in other contexts. This review summarizes the findings from human and animal model systems that provide insight into the factors influencing the expression of these important proteins. We examine the influence of cell cycle and aging as well as genotoxic stress on ING expression levels and evaluate several emerging areas of inquiry demonstrating that ING gene activity may be modulated by factors such as the p53 tumor suppressor, DNA methylation, and ING proteins themselves with external factors such as hormones, reactive oxygen species, TGFbeta signalling, and other proteins of pathological significance also influencing ING levels. We then briefly discuss the influence of post-translational modification and changes in subcellular localization as it pertains to modulation of ING expression. Understanding how ING expression is modulated represents a vital aspect of effective drug targeting strategies.

Cell oxidation-reduction imbalance after modulated radiofrequency radiation.

PubMed

Marjanovic, Ana Marija; Pavicic, Ivan; Trosic, Ivancica

2015-01-01

Aim of this study was to evaluate an influence of modulated radiofrequency field (RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the cell. The assigned RF field was generated within Gigahertz Transversal Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier. Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate was calculated to be 1.6 W/kg. Cell metabolic activity and viability was determined by MTT assay. In order to define total protein content, colorimetric method was used. Concentration of oxidised proteins was evaluated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader device. In comparison with control cell samples, metabolic activity and total protein content in exposed cells did not differ significantly. Concentrations of carbonyl derivates, a product of protein oxidation, insignificantly but continuously increase with duration of exposure. In exposed samples, ROS level significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS level was observed after 30-min treatment indicating antioxidant defence mechanism activation. In conclusion, under the given laboratory conditions, modulated RF radiation might cause impairment in cell oxidation-reduction equilibrium within the growing cells.

Chlorella vulgaris and Pseudomonas putida interaction modulates phosphate trafficking for reduced arsenic uptake in rice (Oryza sativa L.).

PubMed

Srivastava, Suchi; Srivastava, Sonal; Bist, Vidisha; Awasthi, Surabhi; Chauhan, Reshu; Chaudhry, Vasvi; Singh, Poonam C; Dwivedi, Sanjay; Niranjan, Abhishek; Agrawal, Lalit; Chauhan, Puneet Singh; Tripathi, Rudra Deo; Nautiyal, Chandra Shekhar

2018-06-05

Rice grown in arsenic (As) contaminated areas contributes to high dietary exposure of As inducing multiple adverse effects on human health. The As contamination and application of phosphate fertilizers during seedling stage creates a high P and As stress condition. The flooded paddy fields are also conducive for algal growth and microbial activity. The present study proposes potential role of microalgae, Chlorella vulgaris (CHL) and bacteria, Pseudomonas putida (RAR) on rice plant grown under excess As and phosphate (P) conditions. The results show synchronized interaction of CHL + RAR which, reduces As uptake through enhanced P:As and reduced As:biomass ratio by modulating P trafficking. Gene expression analysis of different phosphate transporters exhibited correlation with reduced As uptake and other essential metals. The balancing of reactive oxygen species (ROS), proline accumulation, hormone modulation, and As sequestration in microbial biomass were elucidated as possible mechanisms of As detoxification. The study concludes that RAR and CHL combination mitigates the As stress during P-enriched conditions in rice by: (i) reducing As availability, (ii) modulating the As uptake, and (iii) improving detoxification mechanism of the plant. The study will be important in assessing the role and applicability of P solubilizing biofertilizers in these conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

[Oxidative stress and antioxitant therapy of chronic periodontitis].

PubMed

Shen, Y X; Guo, S J; Wu, Y F

2016-07-01

Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.

Staphyloxanthin photobleaching sensitizes methicillin-resistant Staphylococcus aureus to reactive oxygen species attack

NASA Astrophysics Data System (ADS)

Dong, Pu-Ting; Mohammad, Haroon; Hui, Jie; Wang, Xiaoyu; Li, Junjie; Liang, Lijia; Seleem, Mohamed N.; Cheng, Ji-Xin

2018-02-01

Given that the dearth of new antibiotic development loads an existential burden on successful infectious disease therapy, health organizations are calling for alternative approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report a drug-free photonic approach to eliminate MRSA through photobleaching of staphyloxanthin, an indispensable membrane-bound antioxidant of S. aureus. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by absorption spectroscopy and mass spectrometry, decomposes staphyloxanthin, and sensitizes MRSA to reactive oxygen species attack. Consequently, staphyloxanthin bleaching by low-level blue light eradicates MRSA synergistically with external or internal reactive oxygen species. The effectiveness of this synergistic therapy is validated in MRSA culture, MRSAinfected macrophage cells. Collectively, these findings highlight broad applications of staphyloxanthin photobleaching for treatment of MRSA infections.

Oxidative stress, microRNAs and cytosolic calcium homeostasis.

PubMed

Magenta, Alessandra; Dellambra, Elena; Ciarapica, Roberta; Capogrossi, Maurizio C

2016-09-01

Reactive oxygen species increase cytosolic [Ca(2+)], (Cai), and also modulate the expression of some microRNAs (miRNAs), however the link among oxidative stress, miRNAs and Cai is poorly characterized. In this review we have focused on three groups of miRNAs: (a) miRNAs that are modulated both by ROS and Cai: miR-181a and miR-205; (b) miRNAs that are modulated by ROS and have an effect on Cai: miR-1, miR-21, miR-24, miR-25, miR-185 and miR-214; (c) miRNAs that modulate both ROS and Cai: miR-133; miR-145, miR-495, and we have analyzed their effects on cell signaling and cell function. Finally, in the last section we have examined the role of these miRNAs in the skin, under conditions associated with enhanced oxidative stress, i.e. skin aging, the response to ultraviolet light and two important skin diseases, psoriasis and atopic dermatitis. It is apparent that although some experimental evidence is already available on (a) the role of Cai in miRNAs expression and (b) on the ability of some miRNAs to modulate Cai-dependent intracellular signaling, these research lines are still largely unexplored and represent important areas of future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles.

PubMed

Thirupathi, Anand; Pinho, Ricardo A

2018-05-01

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.

Ligand-induced dynamics of heterotrimeric G protein-coupled receptor-like kinase complexes.

PubMed

Tunc-Ozdemir, Meral; Jones, Alan M

2017-01-01

Arabidopsis, 7-transmembrane Regulator of G signaling protein 1 (AtRGS1) modulates canonical G protein signaling by promoting the inactive state of heterotrimeric G protein complex on the plasma membrane. It is known that plant leucine-rich repeat receptor-like kinases (LRR RLKs) phosphorylate AtRGS1 in vitro but little is known about the in vivo interaction, molecular dynamics, or the cellular consequences of this interaction. Therefore, a subset of the known RLKs that phosphorylate AtRGS1 were selected for elucidation, namely, BAK1, BIR1, FLS2. Several microscopies for both static and dynamic protein-protein interactions were used to follow in vivo interactions between the RLKs and AtRGS1 after the presentation of the Pathogen-associated Molecular Pattern, Flagellin 22 (Flg22). These microscopies included Förster Resonance Energy Transfer, Bimolecular Fluoresence Complementation, and Cross Number and Brightness Fluorescence Correlation Spectroscopy. In addition, reactive oxygen species and calcium changes in living cells were quantitated using luminometry and R-GECO1 microscopy. The LRR RLKs BAK1 and BIR1, interact with AtRGS1 at the plasma membrane. The RLK ligand flg22 sets BAK1 in motion toward AtRGS1 and BIR1 away, both returning to the baseline orientations by 10 minutes. The C-terminal tail of AtRGS1 is important for the interaction with BAK1 and for the tempo of the AtRGS1/BIR1 dynamics. This window of time corresponds to the flg22-induced transient production of reactive oxygen species and calcium release which are both attenuated in the rgs1 and the bak1 null mutants. A temporal model of these interactions is proposed. flg22 binding induces nearly instantaneous dimerization between FLS2 and BAK1. Phosphorylated BAK1 interacts with and enables AtRGS1 to move away from BIR1 and AtRGS1 becomes phosphorylated leading to its endocytosis thus leading to de-repression by permitting AtGPA1 to exchange GDP for GTP. Finally, the G protein complex becomes dissociated thus AGB1 interacts with its effector proteins leading to changes in reactive oxygen species and calcium.

Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic reactive nitrogen formation in mice and in freshly isolated hepatocytes.

PubMed

Banerjee, Sudip; Melnyk, Stepan B; Krager, Kimberly J; Aykin-Burns, Nukhet; McCullough, Sandra S; James, Laura P; Hinson, Jack A

2017-01-01

The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction. In this work we examined the effect of trifluoperazine (TFP), a calmodulin antagonist that inhibits calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen formation in murine hepatocytes and in vivo . In freshly isolated hepatocytes TFP inhibited APAP induced toxicity, reactive nitrogen formation (NO, GSNO, and 3-nitrotyrosine in protein), reactive oxygen formation (superoxide), loss of mitochondrial membrane potential, decreased ATP production, decreased oxygen consumption rate, and increased NADH accumulation. TFP did not alter APAP induced GSH depletion in the hepatocytes or the formation of APAP protein adducts which indicated that reactive metabolite formation was not inhibited. Since we previously reported that TFP inhibits the hepatotoxicity of APAP in mice without altering hepatic APAP-protein adduct formation, we examined the APAP treated mouse livers for evidence of reactive nitrogen formation. 3-Nitrotyrosine in hepatic proteins and GSNO were significantly increased in APAP treated mouse livers and decreased in the livers of mice treated with APAP plus TFP. These data are consistent with a hypothesis that APAP hepatotoxicity occurs with altered calcium metabolism, activation of nNOS leading to increased reactive nitrogen formation, and mitochondrial dysfunction.

Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

NASA Astrophysics Data System (ADS)

Jablonowski, H.; Bussiahn, R.; Hammer, M. U.; Weltmann, K.-D.; von Woedtke, Th.; Reuter, S.

2015-12-01

Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100-400 nm) and, in particular, vacuum ultraviolet (VUV, 10-200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH2O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stable reactive oxygen species, hydrogen peroxide (H2O2) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O2•-) and hydroxyl radicals (•OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.

Continuum-based DFN-consistent numerical framework for the simulation of oxygen infiltration into fractured crystalline rocks

NASA Astrophysics Data System (ADS)

Trinchero, Paolo; Puigdomenech, Ignasi; Molinero, Jorge; Ebrahimi, Hedieh; Gylling, Björn; Svensson, Urban; Bosbach, Dirk; Deissmann, Guido

2017-05-01

We present an enhanced continuum-based approach for the modelling of groundwater flow coupled with reactive transport in crystalline fractured rocks. In the proposed formulation, flow, transport and geochemical parameters are represented onto a numerical grid using Discrete Fracture Network (DFN) derived parameters. The geochemical reactions are further constrained by field observations of mineral distribution. To illustrate how the approach can be used to include physical and geochemical complexities into reactive transport calculations, we have analysed the potential ingress of oxygenated glacial-meltwater in a heterogeneous fractured rock using the Forsmark site (Sweden) as an example. The results of high-performance reactive transport calculations show that, after a quick oxygen penetration, steady state conditions are attained where abiotic reactions (i.e. the dissolution of chlorite and the homogeneous oxidation of aqueous iron(II) ions) counterbalance advective oxygen fluxes. The results show that most of the chlorite becomes depleted in the highly conductive deformation zones where higher mineral surface areas are available for reactions.

Mechanisms of group A Streptococcus resistance to reactive oxygen species

PubMed Central

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

2015-01-01

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the ‘top 10’ causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•−), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

Mechanisms of group A Streptococcus resistance to reactive oxygen species.

PubMed

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

2015-07-01

Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. © FEMS 2015.

Sensitivity of Ca2+ transport of mitochondria to reactive oxygen species.

PubMed

Yang, Z W; Yang, F Y

1997-12-01

The relationship between Ca2+ transport and energy transduction of myocardial mitochondria in the presence of reactive oxygen species was investigated. Following treatment with oxygen free radicals [superoxide(O2.-) or hydroxyl radical (.OH)], lipid free radicals in myocardial mitochondrial membrane could be detected by using the method of EPR spin trap. Simultaneously there were obvious alterations in the free Ca2+ ([Ca2+]m) in the mitochondrial matrix; the physical state of membrane lipid; the efficiency of oxidative phosphorylation (ADP/O); the value of the respiratory control ratio (RCR); and the membrane potential of the inner membrane of myocardial mitochondria. If the concentrations of reactive oxygen species were reduced by about 30%, the alterations in the physical state of the membrane lipid and energy transduction of myocardial mitochondria were not observed, but the changes in Ca2+ homeostasis remained. We conclude that Ca2+ transport by myocardial mitochondria is more sensitive to agents such as O2.- or OH, etc. than are oxidation phosphorylation and the respiratory chain.

FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity.

PubMed

White, M G; Bogdan, R; Fisher, P M; Muñoz, K E; Williamson, D E; Hariri, A R

2012-10-01

Individual variation in physiological responsiveness to stress mediates risk for mental illness and is influenced by both experiential and genetic factors. Common polymorphisms in the human gene for FK506 binding protein 5 (FKBP5), which is involved in transcriptional regulation of the hypothalamic-pituitary-adrenal (HPA) axis, have been shown to interact with childhood abuse and trauma to predict stress-related psychopathology. In the current study, we examined if such gene-environment interaction effects may be related to variability in the threat-related reactivity of the amygdala, which plays a critical role in mediating physiological and behavioral adaptations to stress including modulation of the HPA axis. To this end, 139 healthy Caucasian youth completed a blood oxygen level-dependent functional magnetic resonance imaging probe of amygdala reactivity and self-report assessments of emotional neglect (EN) and other forms of maltreatment. These individuals were genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously associated with psychopathology and/or HPA axis function. Interactions between each SNP and EN emerged such that risk alleles predicted relatively increased dorsal amygdala reactivity in the context of higher EN, even after correcting for multiple testing. Two different haplotype analyses confirmed this relationship as haplotypes with risk alleles also exhibited increased amygdala reactivity in the context of higher EN. Our results suggest that increased threat-related amygdala reactivity may represent a mechanism linking psychopathology to interactions between common genetic variants affecting HPA axis function and childhood trauma. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Impact of physiological noise correction on detecting blood oxygenation level-dependent contrast in the breast

NASA Astrophysics Data System (ADS)

Wallace, Tess E.; Manavaki, Roido; Graves, Martin J.; Patterson, Andrew J.; Gilbert, Fiona J.

2017-01-01

Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance ( Δ R\\text{adj}2   =  3.3  ±  2.1%) and improved the detection of BOLD activation (P  =  0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P  <  0.001). Fluctuations in HR and RVT appeared to be correlated with the stimulus and may contribute to apparent BOLD signal reactivity.

Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic Tumor Oxygenation.

PubMed

Zhu, Piao; Chen, Yu; Shi, Jianlin

2018-04-24

Ultrasound (US)-triggered sonodynamic therapy (SDT) can solve the critical issue of low tissue-penetrating depth of traditional phototriggered therapies, but the SDT efficacy is still not satisfactorily high in combating cancer at the current stage. Here we report on augmenting the SDT efficacy based on catalytic nanomedicine, which takes the efficient catalytic features of nanoenzymes to modulate the tumor microenvironment (TME). The multifunctional nanosonosensitizers have been successfully constructed by the integration of a MnO x component with biocompatible/biodegradable hollow mesoporous organosilica nanoparticles, followed by conjugation with protoporphyrin (as the sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (as the targeting peptide). The MnO x component in the composite nanosonosensitizer acts as an inorganic nanoenzyme for converting the tumor-overexpressed hydrogen peroxide (H 2 O 2 ) molecules into oxygen and enhancing the tumor oxygen level subsequently, which has been demonstrated to facilitate SDT-induced reactive oxygen species production and enhance SDT efficacy subsequently. The targeted accumulation of these composite nanosonosensitizers efficiently suppressed the growth of U87 tumor xenograft on nude mice after US-triggered SDT treatment. The high in vivo biocompatibility and easy excretion of these multifunctional nanosonosensitizers from the body have also been evaluated and demonstrated to guarantee their future clinical translation, and their TME-responsive T 1 -weighted magnetic resonance imaging capability provides the potential for therapeutic guidance and monitoring during SDT.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lepeshkin, Sergey; Baturin, Vladimir; Tikhonov, Evgeny

2016-01-01

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

A mitochondrial redox oxygen sensor in the pulmonary vasculature and ductus arteriosus.

PubMed

Dunham-Snary, Kimberly J; Hong, Zhigang G; Xiong, Ping Y; Del Paggio, Joseph C; Herr, Julia E; Johri, Amer M; Archer, Stephen L

2016-01-01

The mammalian homeostatic oxygen sensing system (HOSS) initiates changes in vascular tone, respiration, and neurosecretion that optimize oxygen uptake and tissue oxygen delivery within seconds of detecting altered environmental or arterial PO2. The HOSS includes carotid body type 1 cells, adrenomedullary cells, neuroepithelial bodies, and smooth muscle cells (SMCs) in pulmonary arteries (PAs), ductus arteriosus (DA), and fetoplacental arteries. Hypoxic pulmonary vasoconstriction (HPV) optimizes ventilation-perfusion matching. In utero, HPV diverts placentally oxygenated blood from the non-ventilated lung through the DA. At birth, increased alveolar and arterial oxygen tension dilates the pulmonary vasculature and constricts the DA, respectively, thereby transitioning the newborn to an air-breathing organism. Though modulated by endothelial-derived relaxing and constricting factors, O2 sensing is intrinsic to PASMCs and DASMCs. Within the SMC's dynamic mitochondrial network, changes in PO2 alter the reduction-oxidation state of redox couples (NAD(+)/NADH, NADP(+)/NADPH) and the production of reactive oxygen species, ROS (e.g., H2O2), by complexes I and III of the electron transport chain (ETC). ROS and redox couples regulate ion channels, transporters, and enzymes, changing intracellular calcium [Ca(2+)]i and calcium sensitivity and eliciting homeostatic responses to hypoxia. In PASMCs, hypoxia inhibits ROS production and reduces redox couples, thereby inhibiting O2-sensitive voltage-gated potassium (Kv) channels, depolarizing the plasma membrane, activating voltage-gated calcium channels (CaL), increasing [Ca(2+)]i, and causing vasoconstriction. In DASMCs, elevated PO2 causes mitochondrial fission, increasing ETC complex I activity and ROS production. The DASMC's downstream response to elevated PO2 (Kv channel inhibition, CaL activation, increased [Ca(2+)]i, and rho kinase activation) is similar to the PASMC's hypoxic response. Impaired O2 sensing contributes to human diseases, including pulmonary arterial hypertension and patent DA.

Reactive Oxygen Species on the Early Earth and Survival of Bacteria

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Oxygen Tension Modulates Differentiation and Primary Macrophage Functions in the Human Monocytic THP-1 Cell Line

PubMed Central

Grodzki, Ana Cristina G.; Giulivi, Cecilia; Lein, Pamela J.

2013-01-01

The human THP-1 cell line is widely used as an in vitro model system for studying macrophage differentiation and function. Conventional culture conditions for these cells consist of ambient oxygen pressure (∼20% v/v) and medium supplemented with the thiol 2-mercaptoethanol (2-ME) and serum. In consideration of the redox activities of O2 and 2-ME, and the extensive experimental evidence supporting a role for reactive oxygen species (ROS) in the differentiation and function of macrophages, we addressed the question of whether culturing THP-1 cells under a more physiologically relevant oxygen tension (5% O2) in the absence of 2-ME and serum would alter THP-1 cell physiology. Comparisons of cultures maintained in 18% O2 versus 5% O2 indicated that reducing oxygen tension had no effect on the proliferation of undifferentiated THP-1 cells. However, decreasing the oxygen tension to 5% O2 significantly increased the rate of phorbol ester-induced differentiation of THP-1 cells into macrophage-like cells as well as the metabolic activity of both undifferentiated and PMA-differentiated THP-1 cells. Removal of both 2-ME and serum from the medium decreased the proliferation of undifferentiated THP-1 cells but increased metabolic activity and the rate of differentiation under either oxygen tension. In differentiated THP-1 cells, lowering the oxygen tension to 5% O2 decreased phagocytic activity, the constitutive release of β-hexosaminidase and LPS-induced NF-κB activation but enhanced LPS-stimulated release of cytokines. Collectively, these data demonstrate that oxygen tension influences THP-1 cell differentiation and primary macrophage functions, and suggest that culturing these cells under tightly regulated oxygen tension in the absence of exogenous reducing agent and serum is likely to provide a physiologically relevant baseline from which to study the role of the local redox environment in regulating THP-1 cell physiology. PMID:23355903

Oxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy.

PubMed

Kulkarni, Aditi C; Kuppusamy, Periannan; Parinandi, Narasimham

2007-10-01

Aerobic life has evolved a dependence on molecular oxygen for its mere survival. Mitochondrial oxidative phosphorylation absolutely requires oxygen to generate the currency of energy in aerobes. The physiologic homeostasis of these organisms is strictly maintained by optimal cellular and tissue-oxygenation status through complex oxygen-sensing mechanisms, signaling cascades, and transport processes. In the event of fluctuating oxygen levels leading to either an increase (hyperoxia) or decrease (hypoxia) in cellular oxygen, the organism faces a crisis involving depletion of energy reserves, altered cell-signaling cascades, oxidative reactions/events, and cell death or tissue damage. Molecular oxygen is activated by both nonenzymatic and enzymatic mechanisms into highly reactive oxygen species (ROS). Aerobes have evolved effective antioxidant defenses to counteract the reactivity of ROS. Although the ROS are also required for many normal physiologic functions of the aerobes, overwhelming production of ROS coupled with their insufficient scavenging by endogenous antioxidants will lead to detrimental oxidative stress. Needless to say, molecular oxygen is at the center of oxygenation, oxidative phosphorylation, and oxidative stress. This review focuses on the biology and pathophysiology of oxygen, with an emphasis on transport, sensing, and activation of oxygen, oxidative phosphorylation, oxygenation, oxidative stress, and oxygen therapy.

Characterization and Reactivity of a Terminal Nickel(III)-Oxygen Adduct

PubMed Central

Pirovano, Paolo; Farquhar, Erik R.; Swart, Marcel; Fitzpatrick, Anthony J.; Morgan, Grace G.; McDonald, Aidan R.

2015-01-01

High-valent terminal metal-oxygen adducts are hypothesized to be the potent oxidising reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel-oxygen adducts are sparse, meaning there is a dearth in the understanding of such oxidants. In this study, a monoanionic NiII-bicarbonate complex was found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (~95%). Electronic absorption, electronic paramagnetic resonance and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S = ½), square planar NiIII-oxygen adduct. This rare example of a high-valent terminal nickel-oxygen complex performs oxidations of organic substrates, including 2,6-ditertbutylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively. PMID:25612563

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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 several configurations with significantly different structures and reactivities. In particular, we find that near the open-circuit potential, non-hydrated hydroxyl is the dominant surface species. On the basis of density functional theory calculations, we show that the removal of hydration enhances the reactivity of oxygen species. Tuning the hydration of hydroxyl near the triple phase boundary will be crucial for designing more active fuel cell cathodes.

Characterization and Reactivity of a Terminal Nickel(III)-Oxygen Adduct

DOE PAGES

Pirovano, Paolo; Farquhar, Erik R.; Swart, Marcel; ...

2015-01-22

Here, high-valent terminal metal–oxygen adducts are hypothesized to be the potent oxidizing reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel–oxygen adducts are scarce, meaning there is a dearth in the understanding of such oxidants. A monoanionic Ni II-bicarbonate complex has been found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (ca. 95%). Electronic absorption, electronic paramagnetic resonance, and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S=1/2), square planar Ni III–oxygen adduct. Moreover, this rare examplemore » of a high-valent terminal nickel–oxygen complex performs oxidations of organic substrates, including 2,6-di-tert-butylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively.« less

Photodynamic immune modulation (PIM)

NASA Astrophysics Data System (ADS)

North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

1999-09-01

Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

Transcription expression of immune-related genes from Caligus rogercresseyi evidences host-dependent patterns on Atlantic and coho salmon.

PubMed

Vera-Bizama, Fredy; Valenzuela-Muñoz, Valentina; Gonçalves, Ana Teresa; Marambio, Jorge Pino; Hawes, Christopher; Wadsworth, Simon; Gallardo-Escárate, Cristian

2015-12-01

The transcriptomic response of the sea louse Caligus rogercresseyi during the infestation on Atlantic salmon (Salmo salar) and coho salmon (Oncorhynchus kisutch) was evaluated using 27 genes related to immune response, antioxidant system and secretome. Results showed early responses of TLR/IMD signaling pathway in sea lice infesting Atlantic salmon. Overall, genes associated with oxidative stress responses were upregulated in both host species. This pattern suggests that reactive oxygen species emitted by the host as a response to the infestation, could modulate the sea louse antioxidant system. Secretome-related transcripts evidenced upregulation of trypsins and serpins, mainly associated to Atlantic salmon than coho salmon. Interestingly, cathepsins and trypsin2 were downregulated at 7 days post-infection (dpi) in coho salmon. The principal component analysis revealed an inverse time-dependent pattern based on the different responses of C. rogercresseyi infecting both salmon species. Here, Atlantic salmon strongly modulates the transcriptome responses at earlier infection stages; meanwhile coho salmon reveals a less marked modulation, increasing the transcription activity during the infection process. This study evidences transcriptome differences between two salmon host species and provides pivotal knowledge towards elaborating future control strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Balaguru, Uma Maheswari; Sundaresan, Lakshmikirupa; Manivannan, Jeganathan; Majunathan, Reji; Mani, Krishnapriya; Swaminathan, Akila; Venkatesan, Saravanakumar; Kasiviswanathan, Dharanibalan; Chatterjee, Suvro

2016-06-01

Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events.

Air pollution induces enhanced mitochondrial oxidative stress in cystic fibrosis airway epithelium.

PubMed

Kamdar, O; Le, Wei; Zhang, J; Ghio, A J; Rosen, G D; Upadhyay, D

2008-10-29

We studied the effects of airborne particulate matters (PM) on cystic fibrosis (CF) epithelium. We noted that PM enhanced human CF bronchial epithelial apoptosis, activated caspase-9 and PARP-1; and reduced mitochondrial membrane potential. Mitochondrial inhibitors (4,4-diisothiocyanatostilbene-2,2'disulfonic acid, rotenone and thenoyltrifluoroacetone) blocked PM-induced generation of reactive oxygen species and apoptosis. PM upregulated pro-apoptotic Bad, Bax, p53 and p21; and enhanced mitochondrial localization of Bax. The anti-apoptotic Bcl-2, Bcl-xl, Mcl-1 and Xiap remained unchanged; however, overexpression of Bcl-xl blocked PM-induced apoptosis. Accordingly, we provide the evidence that PM enhances oxidative stress and mitochondrial signaling mediated apoptosis via the modulation of Bcl family proteins in CF.

Chemical looping coal gasification with calcium ferrite and barium ferrite via solid--solid reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siriwardane, Ranjani; Riley, Jarrett; Tian, Hanjing

Coal gasification to produce synthesis gas by chemical looping was investigated with two oxygen carriers, barium ferrite (BaFe2O4) and calcium ferrite (CaFe2O4). Thermo-gravimetric analysis (TGA) and fixed-bed flow reactor data indicated that a solid–solid interaction occurred between oxygen carriers and coal to produce synthesis gas. Both thermodynamic analysis and experimental data indicated that BaFe2O4 and CaFe2O4 have high reactivity with coal but have a low reactivity with synthesis gas, which makes them very attractive for the coal gasification process. Adding steam increased the production of hydrogen (H2) and carbon monoxide (CO), but carbon dioxide (CO2) remained low because these oxygenmore » carriers have minimal reactivity with H2 and CO. Therefore, the combined steam–oxygen carrier produced the highest quantity of synthesis gas. It appeared that neither the water–gas shift reaction nor the water splitting reaction promoted additional H2 formation with the oxygen carriers when steam was present. Wyodak coal, which is a sub-bituminous coal, had the best gasification yield with oxygen carrier–steam while Illinois #6 coal had the lowest. The rate of gasification and selectivity for synthesis gas production was significantly higher when these oxygen carriers were present during steam gasification of coal. The rates and synthesis gas yields during the temperature ramps of coal–steam with oxygen carriers were better than with gaseous oxygen.« less

[Changes of vascular reactivity and reactive oxygen species in conditions of varying duration of permanent stay in the alienation zone in mice].

PubMed

Tkachenko, M M; Kotsiuruba, A V; Baziliuk, O V; Horot', I V; Sahach, V F

2010-01-01

Peculiarities of changes in the vascular reactivity and in the content of reactive forms of oxygen and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of C57BL/6 and BALB/c mice of the two age groups (6 and 18 mo.), which were born and permanently kept in the Chernobyl alienation zone. The results obtained showed a disturbance of acetylcholine-induced endothelium-dependent reactions of relaxation of smooth muscles of the thoracic aorta. A lower level of NO synthesis and lower level of oxidative arginase metabolism of arginine corresponded to a higher degree of damage of endothelium-dependent reactions of relaxation of the thoracic aorta smooth muscles. A decrease of NO synthesis in conditions of permanent effects of low doses of radiation was conditioned by an increase of generation of reactive forms of oxygen, namely, superoxide and hydroxyl radicals, which might be formed in mitochondria. In conditions of permanent effects of low doses of radiation a lesser level of protein nitrosothilation, same as lesser one of generation of OH-radical, corresponded to a higher level of damage of endothelium-dependent reactions.

Decorative black TiCxOy film fabricated by DC magnetron sputtering without importing oxygen reactive gas

NASA Astrophysics Data System (ADS)

Ono, Katsushi; Wakabayashi, Masao; Tsukakoshi, Yukio; Abe, Yoshiyuki

2016-02-01

Decorative black TiCxOy films were fabricated by dc (direct current) magnetron sputtering without importing the oxygen reactive gas into the sputtering chamber. Using a ceramic target of titanium oxycarbide (TiC1.59O0.31), the oxygen content in the films could be easily controlled by adjustment of total sputtering gas pressure without remarkable change of the carbon content. The films deposited at 2.0 and 4.0 Pa, those are higher pressure when compared with that in conventional magnetron sputtering, showed an attractive black color. In particular, the film at 4.0 Pa had the composition of TiC1.03O1.10, exhibited the L* of 41.5, a* of 0.2 and b* of 0.6 in CIELAB color space. These values were smaller than those in the TiC0.29O1.38 films (L* of 45.8, a* of 1.2 and b* of 1.2) fabricated by conventional reactive sputtering method from the same target under the conditions of gas pressure of 0.3 Pa and optimized oxygen reactive gas concentration of 2.5 vol.% in sputtering gas. Analysis of XRD and XPS revealed that the black film deposited at 4.0 Pa was the amorphous film composed of TiC, TiO and C. The adhesion property and the heat resisting property were enough for decorative uses. This sputtering process has an industrial advantage that the decorative black coating with color uniformity in large area can be easily obtained by plain operation because of unnecessary of the oxygen reactive gas importing which is difficult to be controlled uniformly in the sputtering chamber.

Risk assessment of DNA-reactive carcinogens in food.

PubMed

Jeffrey, A M; Williams, G M

2005-09-01

Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B(1) (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent carcinogen, doses of <1.5 microg of unknown compounds are considered TDIs. Most DNA-reactants, including acrylamide, heterocyclic amines, and alpha,beta-unsaturated carbonyl are below this value. Above that value, measurement of actual DNA adducts levels in either experimental animals with a risk assessment, or, when this occurs, exposed humans are needed. A number of approaches to undertake this are described including immunological, mass spectrometric and (32)P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made.

Risk assessment of DNA-reactive carcinogens in food

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeffrey, A.M.; Williams, G.M.

2005-09-01

Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. Amore » single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B{sub 1} (AFB{sub 1}), a limit of 20 ppb or {approx}30 {mu}g/day has been set and is considered a tolerable daily intake (TDI). Since AFB{sub 1} is considered a potent carcinogen, doses of <1.5 {mu}g of unknown compounds are considered TDIs. Most DNA-reactants, including acrylamide, heterocyclic amines, and {alpha},{beta}-unsaturated carbonyl are below this value. Above that value, measurement of actual DNA adducts levels in either experimental animals with a risk assessment, or, when this occurs, exposed humans are needed. A number of approaches to undertake this are described including immunological, mass spectrometric and {sup 32}P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made.« less

Microfluidic wound bandage: localized oxygen modulation of collagen maturation.

PubMed

Lo, Joe F; Brennan, Martin; Merchant, Zameer; Chen, Lin; Guo, Shujuan; Eddington, David T; DiPietro, Luisa A

2013-01-01

Restoring tissue oxygenation has the potential to improve poorly healing wounds with impaired microvasculature. Compared with more established wound therapy using hyperbaric oxygen chambers, topical oxygen therapy has lower cost and better patient comfort, although topical devices have provided inconsistent results. To provide controlled topical oxygen while minimizing moisture loss, a major issue for topical oxygen, we have devised a novel wound bandage based on microfluidic diffusion delivery of oxygen. In addition to modulating oxygen from 0 to 100% in 60 seconds rise time, the microfluidic oxygen bandage provides a conformal seal around the wound. When 100% oxygen is delivered, it penetrates wound tissues as measured in agar phantom and in vivo wounds. Using this microfluidic bandage, we applied the oxygen modulation to 8 mm excisional wounds prepared on diabetic mice. Treatment with the microfluidic bandage demonstrated improved collagen maturity in the wound bed, although only marginal differences were observed in total collagen, microvasculature, and external closure rates. Our results show that proper topical oxygen can improve wound parameters underneath the surface. Because of the ease of fabrication, the oxygen bandage represents an economical yet practical method for oxygen wound research. © 2013 by the Wound Healing Society.

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

PubMed

Hirai, Daniel M; Jones, Joshua H; Zelt, Joel T; da Silva, Marianne L; Bentley, Robert F; Edgett, Brittany A; Gurd, Brendon J; Tschakovsky, Michael E; O'Donnell, Denis E; Neder, J Alberto

2017-05-01

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N -acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV 1 )-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV 1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo ( P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions ( P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N -acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O 2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD). Copyright © 2017 the American Physiological Society.

Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

PubMed

Gill, Tejpal; Levine, Alan D

2013-09-06

T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

Should modulation of p50 be a therapeutic target in the critically ill?

PubMed

Srinivasan, Amudan J; Morkane, Clare; Martin, Daniel S; Welsby, Ian J

2017-05-01

A defining feature of human hemoglobin is its oxygen binding affinity, quantified by the partial pressure of oxygen at which hemoglobin is 50% saturated (p50), and the variability of this parameter over a range of physiological and environmental states. Modulation of this property of hemoglobin can directly affect the degree of peripheral oxygen offloading and tissue oxygenation. Areas covered: This review summarizes the role of hemoglobin oxygen affinity in normal and abnormal physiology and discusses the current state of the literature regarding artificial modulation of p50. Hypoxic tumors, sickle cell disease, heart failure, and transfusion medicine are discussed in the context of recent advances in hemoglobin oxygen affinity manipulation. Expert commentary: Of particular clinical interest is the possibility of maintaining adequate end-organ oxygen availability in patients with anemia or compromised cardiac function via an increase in systemic p50. This increase in systemic p50 can be achieved with small molecule drugs or a packed red blood cell unit processing variant called rejuvenation, and human trials are needed to better understand the potential clinical benefits to modulating p50.

Dietary Modulation of Oxidative Stress in Alzheimer's Disease.

PubMed

Thapa, Arjun; Carroll, Nick J

2017-07-21

Cells generate unpaired electrons, typically via oxygen- or nitrogen-based by-products during normal cellular respiration and under stressed situations. These pro-oxidant molecules are highly unstable and may oxidize surrounding cellular macromolecules. Under normal conditions, the reactive oxygen or nitrogen species can be beneficial to cell survival and function by destroying and degrading pathogens or antigens. However, excessive generation and accumulation of the reactive pro-oxidant species over time can damage proteins, lipids, carbohydrates, and nucleic acids. Over time, this oxidative stress can contribute to a range of aging-related degenerative diseases such as cancer, diabetes, macular degeneration, and Alzheimer's, and Parkinson's diseases. It is well accepted that natural compounds, including vitamins A, C, and E, β-carotene, and minerals found in fruits and vegetables are powerful anti-oxidants that offer health benefits against several different oxidative stress induced degenerative diseases, including Alzheimer's disease (AD). There is increasing interest in developing anti-oxidative therapeutics to prevent AD. There are contradictory and inconsistent reports on the possible benefits of anti-oxidative supplements; however, fruits and vegetables enriched with multiple anti-oxidants (e.g., flavonoids and polyphenols) and minerals may be highly effective in attenuating the harmful effects of oxidative stress. As the physiological activation of either protective or destructive pro-oxidant behavior remains relatively unclear, it is not straightforward to relate the efficacy of dietary anti-oxidants in disease prevention. Here, we review oxidative stress mediated toxicity associated with AD and highlight the modulatory roles of natural dietary anti-oxidants in preventing AD.

Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases.

PubMed

Wang, Yating; Wei, Sixi; Wang, Jishi; Fang, Qin; Chai, Qixiang

2014-07-01

Phenethyl isothiocyanate (PEITC), a potential cancer chemopreventive constituent of cruciferous vegetables, including watercress, has been reported to inhibit cancer cell growth by arresting the cell cycle and inducing apoptosis in various human cancer cell models. However, the role of PEITC in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms have yet to be elucidated. In the present study, PEITC was found to induce cell death through the induction of reactive oxygen species (ROS) stress and oxidative damage. Heme oxygenase‑1 (HO‑1), which participates in the development of numerous tumors and the sensitivity of these tumors to chemotherapeutic drugs, plays a protective role by modulating oxidative injury. Therefore, the present study assessed the inhibitory effect of PEITC on K562 cells and whether HO‑1 facilitated cell apoptosis and ROS generation. PEITC was found to suppress cell growth and cause apoptosis by promoting Fas and Fas ligand expression, increasing ROS generation and by the successive release of cytochrome c as well as the activation of caspase‑9 and caspase‑3. PEITC was also combined with the HO‑1 inhibitor zinc protoporphyrin IX and the inducer hemin to assess whether HO‑1 determines cell survival and ROS generation. The results of the present study suggest that PEITC may be a potential anti‑tumor compound for CML therapy, and that HO‑1 has a critical function in PEITC‑induced apoptosis and ROS generation.

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

PubMed Central

Rubio, Noemi; Coupienne, Isabelle; Di Valentin, Emmanuel; Heirman, Ingeborg; Grooten, Johan; Piette, Jacques; Agostinis, Patrizia

2012-01-01

Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis. PMID:22889744

Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells

PubMed Central

Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

2018-01-01

Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (−48%, p < 0.001) and disruption of insulin secretion (p < 0.001) associated with of reactive oxygen species (ROS) production and a modulation of pro-oxidant and antioxidant signaling pathway. Cell pre-treatments with extracts considerably increased cell viability (+86% p < 0.001) for simmondsin and +74% (p < 0.001) for aqueous extract and insulin secretion. The extracts also markedly decreased ROS (−69% (p < 0.001) for simmondsin and −59% (p < 0.001) for aqueous extract) and caspase-3 activation and improved antioxidant defense, inhibiting p22phox and increasing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) levels (+70%, p < 0.001) for aqueous extract. Simmondsin had no impact on Nrf2 levels. The richness and diversity of molecules present in jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia. PMID:29558444

The RING finger E3 ligase STRF1 is involved in membrane trafficking and modulates salt-stress response in Arabidopsis thaliana.

PubMed

Tian, Miaomiao; Lou, Lijuan; Liu, Lijing; Yu, Feifei; Zhao, Qingzhen; Zhang, Huawei; Wu, Yaorong; Tang, Sanyuan; Xia, Ran; Zhu, Baoge; Serino, Giovanna; Xie, Qi

2015-04-01

Salt stress is a detrimental factor for plant growth and development. The response to salt stress has been shown to involve components in the intracellular trafficking system, as well as components of the ubiquitin-proteasome system (UPS). In this article, we have identified in Arabidopsis thaliana a little reported ubiquitin ligase involved in salt-stress response, which we named STRF1 (Salt Tolerance RING Finger 1). STRF1 is a member of RING-H2 finger proteins and we demonstrate that it has ubiquitin ligase activity in vitro. We also show that STRF1 localizes mainly at the plasma membrane and at the intracellular endosomes. strf1-1 loss-of-function mutant seedlings exhibit accelerated endocytosis in roots, and have altered expression of several genes involved in the membrane trafficking system. Moreover, protein trafficking inhibitor, brefeldin A (BFA), treatment has increased BFA bodies in strf1-1 mutant. This mutant also showed increased tolerance to salt, ionic and osmotic stresses, reduced accumulation of reactive oxygen species during salt stress, and increased expression of AtRbohD, which encodes a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase involved in H2 O2 production. We conclude that STRF1 is a membrane trafficking-related ubiquitin ligase, which helps the plant to respond to salt stress by monitoring intracellular membrane trafficking and reactive oxygen species (ROS) production. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

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

PubMed

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

2017-04-01

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

The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma.

PubMed

Stafford, Phillip; Abdelwahab, Mohammed G; Kim, Do Young; Preul, Mark C; Rho, Jong M; Scheck, Adrienne C

2010-09-10

Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia. Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet. Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4. Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

Shoot phytochrome B modulates reactive oxygen species homeostasis in roots via abscisic acid signaling in Arabidopsis.

PubMed

Ha, Jun-Ho; Kim, Ju-Heon; Kim, Sang-Gyu; Sim, Hee-Jung; Lee, Gisuk; Halitschke, Rayko; Baldwin, Ian T; Kim, Jeong-Il; Park, Chung-Mo

2018-06-01

Underground roots normally reside in darkness. However, they are often exposed to ambient light that penetrates through cracks in the soil layers which can occur due to wind, heavy rain or temperature extremes. In response to light exposure, roots produce reactive oxygen species (ROS) which promote root growth. It is known that ROS-induced growth promotion facilitates rapid escape of the roots from non-natural light. Meanwhile, long-term exposure of the roots to light elicits a ROS burst, which causes oxidative damage to cellular components, necessitating that cellular levels of ROS should be tightly regulated in the roots. Here we demonstrate that the red/far-red light photoreceptor phytochrome B (phyB) stimulates the biosynthesis of abscisic acid (ABA) in the shoots, and notably the shoot-derived ABA signals induce a peroxidase-mediated ROS detoxification reaction in the roots. Accordingly, while ROS accumulate in the roots of the phyb mutant that exhibits reduced primary root growth in the light, such an accumulation of ROS did not occur in the dark-grown phyb roots that exhibited normal growth. These observations indicate that mobile shoot-to-root ABA signaling links shoot phyB-mediated light perception with root ROS homeostasis to help roots adapt to unfavorable light exposure. We propose that ABA-mediated shoot-to-root phyB signaling contributes to the synchronization of shoot and root growth for optimal propagation and performance in plants. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

PubMed

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

Dihydroartemisinin Enhances Apo2L/TRAIL-Mediated Apoptosis in Pancreatic Cancer Cells via ROS-Mediated Up-Regulation of Death Receptor 5

PubMed Central

Cheng, Zhuo-xin; Wang, Yong-wei; Mu, Ming; Wang, Shuang-jia; Pan, Shang-ha; Gao, Yue; Jiang, Hong-chi; Dong, De-li; Sun, Bei

2012-01-01

Background Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded as a promising anticancer agent, but chemoresistance affects its efficacy as a treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL has not been well documented, and the mechanisms involved remain unclear. Methodology/Principal Findings Here, we report that DHA enhances the efficacy of Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was mediated through the generation of reactive oxygen species, the induction of death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small interfering RNA also significantly reduced the amount of apoptosis induced by DHA and Apo2L/TRAIL. Conclusions/Significance These results suggest that DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through reactive oxygen species-mediated up-regulation of DR5. PMID:22666346

Molecular Mechanisms of Action and Therapeutic Uses of Pharmacological Inhibitors of HIF–Prolyl 4-Hydroxylases for Treatment of Ischemic Diseases

PubMed Central

Selvaraju, Vaithinathan; Parinandi, Narasimham L.; Adluri, Ram Sudheer; Goldman, Joshua W.; Hussain, Naveed; Sanchez, Juan A.

2014-01-01

Abstract Significance: In this review, we have discussed the efficacy and effect of small molecules that act as prolyl hydroxylase domain inhibitors (PHDIs). The use of these compounds causes upregulation of the pro-angiogenic factors and hypoxia inducible factor-1α and -2α (HIF-1α and HIF-2α) to enhance angiogenic, glycolytic, erythropoietic, and anti-apoptotic pathways in the treatment of various ischemic diseases responsible for significant morbidity and mortality in humans. Recent Advances: Sprouting of new blood vessels from the existing vasculature and surgical intervention, such as coronary bypass and stent insertion, have been shown to be effective in attenuating ischemia. However, the initial reentry of oxygen leads to the formation of reactive oxygen species that cause oxidative stress and result in ischemia/reperfusion (IR) injury. This apparent “oxygen paradox” must be resolved to combat IR injury. During hypoxia, decreased activity of PHDs initiates the accumulation and activation of HIF-1α, wherein the modulation of both PHD and HIF-1α appears as promising therapeutic targets for the pharmacological treatment of ischemic diseases. Critical Issues: Research on PHDs and HIFs has shown that these molecules can serve as therapeutic targets for ischemic diseases by modulating glycolysis, erythropoiesis, apoptosis, and angiogenesis. Efforts are underway to identify and synthesize safer small-molecule inhibitors of PHDs that can be administered in vivo as therapy against ischemic diseases. Future Directions: This review presents a comprehensive and current account of the existing small-molecule PHDIs and their use in the treatment of ischemic diseases with a focus on the molecular mechanisms of therapeutic action in animal models. Antioxid. Redox Signal. 20, 2631–2665. PMID:23992027

Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular Interactions

PubMed Central

Said, Ahmed S.; Rogers, Stephen C.; Doctor, Allan

2018-01-01

Here, we review current data elucidating the role of red blood cell derived microparticles (RMPs) in normal vascular physiology and disease progression. Microparticles (MPs) are submicron-size, membrane-encapsulated vesicles derived from various parent cell types. MPs are produced in response to numerous stimuli that promote a sequence of cytoskeletal and membrane phospholipid changes and resulting MP genesis. MPs were originally considered as potential biomarkers for multiple disease processes and more recently are recognized to have pleiotropic biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in initiating apoptosis. RMPs, specifically, form normally during RBC maturation in response to injury during circulation, and are copiously produced during processing and storage for transfusion. Notably, several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs markedly from that of intact RBCs and the nature/composition of RMP components are affected by the specific circumstances of RMP genesis. Described RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion as well as influence upon vasoregulation via influence upon nitric oxide (NO) bioavailability. Of particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this physiology has been proposed to contribute to the impaired oxygen delivery homeostasis that may be observed following transfusion. In summary, RMPs are submicron particles released from RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in normal and patho-physiology and in transfusion recipients is an area of continued investigation. PMID:29379445

Influence of red blood cell-derived microparticles upon vasoregulation

PubMed Central

Said, Ahmed S.; Doctor, Allan

2017-01-01

Here we review recent data and the evolving understanding of the role of red blood cell-derived microparticles (RMPs) in normal physiology and in disease progression. Microparticles (MPs) are small membrane vesicles derived from various parent cell types. MPs are produced in response to a variety of stimuli through several cytoskeletal and membrane phospholipid changes. MPs have been investigated as potential biomarkers for multiple disease processes and are thought to have biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in apoptosis. Specifically, RMPs are produced normally during RBC maturation and their production is accelerated during processing and storage for transfusion. Several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs from that of intact RBCs, and the nature and composition of RMP components are affected by both storage duration and the character of storage solutions. Recognised RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion, as well as influence upon vasoregulation via nitric oxide (NO) scavenging. Of particular relevance, RMPs are more avid NO scavengers than intact RBCs and this feature has been proposed as a mechanism for the impaired oxygen delivery homeostasis that has been observed following transfusion. Preliminary human studies demonstrate that circulating RMP abundance increases with RBC transfusion and is associated with altered plasma vasoactivity and abnormal vasoregulation. In summary, RMPs are submicron particles released from stored RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in transfusion recipients is an area of continued investigation. PMID:28686154

Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular Interactions.

PubMed

Said, Ahmed S; Rogers, Stephen C; Doctor, Allan

2017-01-01

Here, we review current data elucidating the role of red blood cell derived microparticles (RMPs) in normal vascular physiology and disease progression. Microparticles (MPs) are submicron-size, membrane-encapsulated vesicles derived from various parent cell types. MPs are produced in response to numerous stimuli that promote a sequence of cytoskeletal and membrane phospholipid changes and resulting MP genesis. MPs were originally considered as potential biomarkers for multiple disease processes and more recently are recognized to have pleiotropic biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in initiating apoptosis. RMPs, specifically, form normally during RBC maturation in response to injury during circulation, and are copiously produced during processing and storage for transfusion. Notably, several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs markedly from that of intact RBCs and the nature/composition of RMP components are affected by the specific circumstances of RMP genesis. Described RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion as well as influence upon vasoregulation via influence upon nitric oxide (NO) bioavailability. Of particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this physiology has been proposed to contribute to the impaired oxygen delivery homeostasis that may be observed following transfusion. In summary, RMPs are submicron particles released from RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in normal and patho-physiology and in transfusion recipients is an area of continued investigation.

Influence of red blood cell-derived microparticles upon vasoregulation.

PubMed

Said, Ahmed S; Doctor, Allan

2017-10-01

Here we review recent data and the evolving understanding of the role of red blood cell-derived microparticles (RMPs) in normal physiology and in disease progression. Microparticles (MPs) are small membrane vesicles derived from various parent cell types. MPs are produced in response to a variety of stimuli through several cytoskeletal and membrane phospholipid changes. MPs have been investigated as potential biomarkers for multiple disease processes and are thought to have biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in apoptosis. Specifically, RMPs are produced normally during RBC maturation and their production is accelerated during processing and storage for transfusion. Several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs from that of intact RBCs, and the nature and composition of RMP components are affected by both storage duration and the character of storage solutions. Recognised RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion, as well as influence upon vasoregulation via nitric oxide (NO) scavenging. Of particular relevance, RMPs are more avid NO scavengers than intact RBCs and this feature has been proposed as a mechanism for the impaired oxygen delivery homeostasis that has been observed following transfusion. Preliminary human studies demonstrate that circulating RMP abundance increases with RBC transfusion and is associated with altered plasma vasoactivity and abnormal vasoregulation. In summary, RMPs are submicron particles released from stored RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in transfusion recipients is an area of continued investigation.

Dietary antioxidants and exercise.

PubMed

Powers, Scott K; DeRuisseau, Keith C; Quindry, John; Hamilton, Karyn L

2004-01-01

Muscular exercise promotes the production of radicals and other reactive oxygen species in the working muscle. Growing evidence indicates that reactive oxygen species are responsible for exercise-induced protein oxidation and contribute to muscle fatigue. To protect against exercise-induced oxidative injury, muscle cells contain complex endogenous cellular defence mechanisms (enzymatic and non-enzymatic antioxidants) to eliminate reactive oxygen species. Furthermore, exogenous dietary antioxidants interact with endogenous antioxidants to form a cooperative network of cellular antioxidants. Knowledge that exercise-induced oxidant formation can contribute to muscle fatigue has resulted in numerous investigations examining the effects of antioxidant supplementation on human exercise performance. To date, there is limited evidence that dietary supplementation with antioxidants will improve human performance. Furthermore, it is currently unclear whether regular vigorous exercise increases the need for dietary intake of antioxidants. Clearly, additional research that analyses the antioxidant requirements of individual athletes is needed.

Mechanisms of lectin and antibody-dependent polymorphonuclear leukocyte-mediated cytolysis.

PubMed

Tsunawaki, S; Ikenami, M; Mizuno, D; Yamazaki, M

1983-04-01

The mechanisms of tumor lysis by polymorphonuclear leukocytes (PMNs) were investigated. In antibody-dependent PMN-mediated cytolysis (ADPC), sensitized tumor cells were specifically lysed via Fc receptors on PMNs. On the other hand, lectin-dependent PMN-mediated cytolysis (LDPC) caused nonspecific lysis of several murine tumors after recognition of carbohydrate moieties on the cell membrane of both PMNs and tumor cells. Both ADPC and LDPC depended on glycolysis, and cytotoxicity was mediated by reactive oxygen species; LDPC was dependent on superoxide and ADPC on the myeloperoxidase system. The participation of reactive oxygen species in PMN cytotoxicity was also demonstrated by pharmacological triggering with phorbol myristate acetate. These results indicate that reactive oxygen species have an important role In tumor killing by PMNs and that ADPC and LDPC have partly different cytolytic processes as well as different recognition steps.

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production.

PubMed

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis . Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis . More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress.

Induction of Tca8113 tumor cell apoptosis by icotinib is associated with reactive oxygen species mediated p38-MAPK activation.

PubMed

Yang, Cailing; Yan, Jianguo; Yuan, Guoyan; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Cui, Weigang

2014-08-01

Icotinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), has been shown to exhibit anti-tumor activity against several tumor cell lines. However, the exact molecular mechanism of icotinib's anti-tumor effect remains unknown. This study aims to examine the zytotoxic effect of icotinib on Tca8113 cells and its potential molecular mechanism. Icotinib significantly resulted in dose-dependent cell death as determined by MTT assay, accompanied by increased levels of Bax and DNA fragmentation. Icotinib could also induce Reactive Oxygen Species (ROS) generation. Further studies confirmed that scavenging of reactive oxygen species by N-acetyl-L-cysteine (NAC), and pharmacological inhibition of MAPK reversed icotinib-induced apoptosis in Tca8113 cells. Our data provide evidence that icotinib induces apoptosis, possibly via ROS-mediated MAPK pathway in Tca8113 cells.

Trojan Horse for Light-Triggered Bifurcated Production of Singlet Oxygen and Fenton-Reactive Iron within Cancer Cells.

PubMed

Cioloboc, Daniela; Kennedy, Christopher; Boice, Emily N; Clark, Emily R; Kurtz, Donald M

2018-01-08

Traditional photodynamic therapy for cancer relies on dye-photosensitized generation of singlet oxygen. However, therapeutically effective singlet oxygen generation requires well-oxygenated tissues, whereas many tumor environments tend to be hypoxic. We describe a platform for targeted enhancement of photodynamic therapy that produces singlet oxygen in oxygenated environments and hydroxyl radical, which is typically regarded as the most toxic reactive oxygen species, in hypoxic environments. The 24-subunit iron storage protein bacterioferritin (Bfr) has the unique property of binding 12 heme groups in its protein shell. We inserted the isostructural photosensitizer, zinc(II) protoporphyrin IX (ZnP), in place of the hemes and extended the surface-exposed N-terminal ends of the Bfr subunits with a peptide targeting a receptor that is hyperexpressed on the cell surface of many tumors and tumor vasculature. We then loaded the inner cavity with ∼2500 irons as a ferric oxyhydroxide polymer and finally conjugated 2 kDa polyethylene glycol to the outer surface. We showed that the inserted ZnP photosensitizes generation of both singlet oxygen and the hydroxyl radical, the latter via the reaction of photoreleased ferrous iron with hydrogen peroxide. This targeted iron-loaded ZnP-Bfr construct was endocytosed by C32 melanoma cells and localized to lysosomes. Irradiating the treated cells with light at wavelengths overlapping the ZnP Soret absorption band induced photosensitized intracellular Fe 2+ release and substantial lowering of cell viability. This targeted, light-triggered production of intracellular singlet oxygen and Fenton-reactive iron could potentially be developed into a phototherapeutic adjunct for many types of cancers.

A novel anti-theft security system for photovoltaic modules

NASA Astrophysics Data System (ADS)

Khan, Wasif Ali; Lim, Boon-Han; Lai, An-Chow; Chong, Kok-Keong

2017-04-01

Solar farms are considered as easy target for thieves because of insufficient protection measures. Existing anti-theft approaches are based on system level and are not very preventive and efficient because these can be bypassed with some technical knowledge. Additionally, it is difficult for security guards to tackle them as robbers come in a form of a gang equipped with heavy weapons. In this paper, a low power auto shut-off and non-destructive system is proposed for photovoltaic (PV) modules to achieve better level of security at module level. In proposed method, the power generation function of the PV module will be shut-off internally and cannot be re-activated by unauthorized personnel, in the case of theft. Hence, the PV module will not be functional even sold to new customers. The system comprises of a microcontroller, a low power position sensor, a controllable semiconductor switch and a wireless reactive-able system. The anti-theft system is developed to be laminated inside PV module and will be interconnected with solar cells so it becomes difficult for thieves to temper. The position of PV module is retrieved by position sensor and stored in a microcontroller as an initial reference value. Microcontroller uses this stored reference value to control power supply of PV module via power switch. The stored reference value can be altered using wireless circuitry by following authentication protocol. It makes the system non-destructive as anti-theft function can be reset again by authorized personnel, if it is recovered after theft or moved for maintenance purposes. The research component includes the design of a position sensing circuit, an auto shut-off circuit, a reactive-able wireless security protection algorithm and finally the integration of the multiple circuits.

Reactive oxygen species generation and signaling in plants

PubMed Central

Tripathy, Baishnab Charan; Oelmüller, Ralf

2012-01-01

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

Glutathionylation acts as a control switch for uncoupling proteins UCP2 and UCP3.

PubMed

Mailloux, Ryan J; Seifert, Erin L; Bouillaud, Frédéric; Aguer, Céline; Collins, Sheila; Harper, Mary-Ellen

2011-06-17

The mitochondrial uncoupling proteins 2 and 3 (UCP2 and -3) are known to curtail oxidative stress and participate in a wide array of cellular functions, including insulin secretion and the regulation of satiety. However, the molecular control mechanism(s) governing these proteins remains elusive. Here we reveal that UCP2 and UCP3 contain reactive cysteine residues that can be conjugated to glutathione. We further demonstrate that this modification controls UCP2 and UCP3 function. Both reactive oxygen species and glutathionylation were found to activate and deactivate UCP3-dependent increases in non-phosphorylating respiration. We identified both Cys(25) and Cys(259) as the major glutathionylation sites on UCP3. Additional experiments in thymocytes from wild-type and UCP2 null mice demonstrated that glutathionylation similarly diminishes non-phosphorylating respiration. Our results illustrate that UCP2- and UCP3-mediated state 4 respiration is controlled by reversible glutathionylation. Altogether, these findings advance our understanding of the roles UCP2 and UCP3 play in modulating metabolic efficiency, cell signaling, and oxidative stress processes.

Reactively sputtered thermochromic tungsten-doped VO2 films

NASA Astrophysics Data System (ADS)

Sobhan, M. A.; Kivaisi, R. T.; Stjerna, B. A.; Granqvist, Claes-Goeran

1994-09-01

Tungsten-doped vanadium oxide (V1-xWxO2) films were prepared by concurrent reactive dc magnetron sputtering of vanadium and tungsten in an Ar + O2 plasma with a controlled oxygen partial pressure. Films were deposited onto glass substrates at 400 degree(s)C. The films had a metal-semiconductor transition at a temperature (tau) t that was depressed when x was increased. Rutherford Back Scattering was used to determine x. X- ray diffraction was employed to confirm the monoclinic low-temperature VO2 phase. The relation between x and (tau) t was studied and compared with results from the literature. It was shown that (tau) t could be set to a value between 17 and 65 degree(s)C by proper choice of x. The optical and electrical properties of the films were investigated around the metal-semiconductor phase transition. The luminous transmittance was rather unaffected by the temperature, whereas the near infrared transmittance showed lower values above (tau) t. The degree of thermochromic modulation decreased for increased x. Electrical measurements showed that the ratio of the resistance above and below (tau) t decreased with increasing x.

Molybdenum disulfide for ultra-low detection of free radicals: electrochemical response and molecular modeling

NASA Astrophysics Data System (ADS)

Gupta, Ankur; Rawal, Takat B.; Neal, Craig J.; Das, Soumen; Rahman, Talat S.; Seal, Sudipta

2017-06-01

Two-dimensional (2D) molybdenum disulfide (MoS2) offers attractive properties due to its band gap modulation and has led to significant research-oriented applications (i.e. DNA and protein detection, cell imaging (fluorescent label) etc.). In biology, detection of free radicals (i.e. reactive oxygen species and reactive nitrogen (NO*) species are very important for early discovery and treatment of diseases. Herein, for the first time, we demonstrate the ultra-low (pico-molar) detection of pharmaceutically relevant free radicals using MoS2 for electrochemical sensing. We present pico- to nano- molar level sensitivity in smaller MoS2 with S-deficiency as revealed by x-ray photoelectron spectroscopy. Furthermore, the detection mechanism and size-dependent sensitivity have been investigated by density functional theory (DFT) showing the change in electronic density of states of Mo atoms at edges which lead to the preferred adsorption of H2O2 on Mo edges. The DFT analysis signifies the role of size and S-deficiency in the higher catalytic activity of smaller MoS2 particles and, thus, ultra-low detection.

Quantum indistinguishability in chemical reactions.

PubMed

Fisher, Matthew P A; Radzihovsky, Leo

2018-05-15

Quantum indistinguishability plays a crucial role in many low-energy physical phenomena, from quantum fluids to molecular spectroscopy. It is, however, typically ignored in most high-temperature processes, particularly for ionic coordinates, implicitly assumed to be distinguishable, incoherent, and thus well approximated classically. We explore enzymatic chemical reactions involving small symmetric molecules and argue that in many situations a full quantum treatment of collective nuclear degrees of freedom is essential. Supported by several physical arguments, we conjecture a "quantum dynamical selection" (QDS) rule for small symmetric molecules that precludes chemical processes that involve direct transitions from orbitally nonsymmetric molecular states. As we propose and discuss, the implications of the QDS rule include ( i ) a differential chemical reactivity of para- and orthohydrogen, ( ii ) a mechanism for inducing intermolecular quantum entanglement of nuclear spins, ( iii ) a mass-independent isotope fractionation mechanism, ( iv ) an explanation of the enhanced chemical activity of "reactive oxygen species", ( v ) illuminating the importance of ortho-water molecules in modulating the quantum dynamics of liquid water, and ( vi ) providing the critical quantum-to-biochemical linkage in the nuclear spin model of the (putative) quantum brain, among others.

Direct detection of free radicals and reactive oxygen species in thylakoids.

PubMed

Hideg, Eva; Kálai, Tamás; Hideg, Kálmán

2011-01-01

In plants, reactive oxygen species (ROS), also known as active oxygen species (AOS), are associated with normal, physiologic processes as well as with responses to adverse conditions. ROS are connected to stress in many ways: as primary elicitors, as products and propagators of oxidative damage, or as signal molecules initiating defense or adaptation. The photosynthetic electron transport is a major site of oxidative stress by visible or ultraviolet light, high or low temperature, pollutants or herbicides. ROS production can be presumed from detecting oxidatively damaged lipids, proteins, or pigments as well as from the alleviating effects of added antioxidants. On the contrary, measuring ROS by special sensor molecules provides more direct information. This chapter focuses on the application of spin trapping electron paramagnetic resonance (EPR) spectroscopy for detecting ROS: singlet oxygen and oxygen free radicals in thylakoid membrane preparations.

Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

PubMed Central

Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

2017-01-01

Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a paradoxical effect of antioxidant therapy to exacerbate arterial remodeling in animals with severe pulmonary arterial hypertension in the hypoxia/SU5416 model. PMID:28666030

Effects of methyltestosterone on immunity against Salmonella Pullorum in dwarf chicks.

PubMed

Li, H; Zhang, Y; Zuo, S F; Lian, Z X; Li, N

2009-12-01

This study was conducted to determine effects of methyltestosterone on innate immunity and adaptive immunity against Salmonella Pullorum in dwarf chicks. In vivo experiment, comparisons of pathological sections, viable counts of bacteria, specific antibody levels, and subsets of T lymphocytes were set forth between chicks with or without 10(-7) M methyltestosterone treatment (2 d of age through 21 d of age) and challenged with 5 x 10(8) virulent Salmonella Pullorum (7 d of age), and in vitro experiment, phagocytic and killing abilities, reactive oxygen intermediate production, and reactive nitrogen intermediate production of monocytes-macrophages treated with high (10(-8) M/10(6) cell) or physiological (10(-14) M/10(6) cell) concentration of methyltestosterone were examined after Salmonella Pullorum infection. The results showed that (1) in vivo, administration of methyltestosterone enhanced susceptibility to Salmonella Pullorum infection and depressed cellular immunity against Salmonella Pullorum, whereas it had no effect on humoral immunity in dwarf chicks; (2) in vitro, at high concentration, methyltestosterone reduced (P < 0.05) monocytes-macrophages mediated reactive oxygen intermediate-dependent killing of Salmonella Pullorum, whereas low concentration of methyltestosterone enhanced (P < 0.05) reactive oxygen intermediate-dependent killing of Salmonella Pullorum in male dwarf chicks but not in females; and (3) although challenged with Salmonella Pullorum, phagocytic ability and monocytes-macrophages mediated reactive nitrogen intermediate-dependent killing were not affected by methyltestosterone in vitro. The results indicated that methyltestosterone affected the immune response to Salmonella Pullorum in dwarf chicks by changing monocytes-macrophages mediated reactive oxygen intermediate-dependent killing and cellular immunity, and the effects were dose-dependent; furthermore, the former 2 pathways played important roles in preventing Salmonella Pullorum infection in dwarf chicks, although the mechanism needs further study.

The [NiFe]-Hydrogenase of Pyrococcus furiosus Exhibits a New Type of Oxygen Tolerance.

PubMed

Kwan, Patrick; McIntosh, Chelsea L; Jennings, David P; Hopkins, R Chris; Chandrayan, Sanjeev K; Wu, Chang-Hao; Adams, Michael W W; Jones, Anne K

2015-10-28

We report the first direct electrochemical characterization of the impact of oxygen on the hydrogen oxidation activity of an oxygen-tolerant, group 3, soluble [NiFe]-hydrogenase: hydrogenase I from Pyrococcus furiosus (PfSHI), which grows optimally near 100 °C. Chronoamperometric experiments were used to probe the sensitivity of PfSHI hydrogen oxidation activity to both brief and prolonged exposure to oxygen. For experiments between 15 and 80 °C, following short (<200 s) exposure to 14 μM O2 under oxidizing conditions, PfSHI always maintains some fraction of its initial hydrogen oxidation activity; i.e., it is oxygen-tolerant. Reactivation experiments show that two inactive states are formed by interaction with oxygen and both can be quickly (<150 s) reactivated. Analogous experiments, in which the interval of oxygen exposure is extended to 900 s, reveal that the response is highly temperature-dependent. At 25 °C, under sustained 1% O2/ 99% H2 exposure, the H2oxidation activity drops nearly to zero. However, at 80 °C, up to 32% of the enzyme's oxidation activity is retained. Reactivation of PfSHI following sustained exposure to oxygen occurs on a much longer time scale (tens of minutes), suggesting that a third inactive species predominates under these conditions. These results stand in contrast to the properties of oxygen-tolerant, group 1 [NiFe]-hydrogenases, which form a single state upon reaction with oxygen, and we propose that this new type of hydrogenase should be referred to as oxygen-resilient. Furthermore, PfSHI, like other group 3 [NiFe]-hydrogenases, does not possess the proximal [4Fe3S] cluster associated with the oxygen tolerance of some group 1 enzymes. Thus, a new mechanism is necessary to explain the observed oxygen tolerance in soluble, group 3 [NiFe]-hydrogenases, and we present a model integrating both electrochemical and spectroscopic results to define the relationships of these inactive states.

Ceramic oxygen transport membrane array reactor and reforming method

DOEpatents

Kelly, Sean M.; Christie, Gervase Maxwell; Rosen, Lee J.; Robinson, Charles; Wilson, Jamie R.; Gonzalez, Javier E.; Doraswami, Uttam R.

2016-09-27

A commercially viable modular ceramic oxygen transport membrane reforming reactor for producing a synthesis gas that improves the thermal coupling of reactively-driven oxygen transport membrane tubes and catalyst reforming tubes required to efficiently and effectively produce synthesis gas.

Environmental Health Hazards of e-Cigarettes and their Components: Oxidants and Copper in e-cigarette aerosols

PubMed Central

Lerner, Chad A.; Sundar, Isaac K.; Watson, Richard M.; Elder, Alison; Jones, Ryan; Done, Douglas; Kurtzman, Rachel; Ossip, Deborah J.; Robinson, Risa; McIntosh, Scott; Rahman, Irfan

2014-01-01

To narrow the gap in our understanding of potential oxidative properties associated with Electronic Nicotine Delivery systems (ENDS) i.e. e-cigarettes, we employed semi-quantitative methods to detect oxidant reactivity in disposable components of ENDS/e-cigarettes (batteries and cartomizers) using a fluorescein indicator. These components exhibit oxidants/reactive oxygen species reactivity similar to used conventional cigarette filters. Oxidants/reactive oxygen species reactivity in e-cigarette aerosols was also similar to oxidant reactivity in cigarette smoke. A cascade particle impactor allowed sieving of a range of particle size distributions between 0.450 and 2.02 μm in aerosols from an e-cigarette. Copper, being among these particles, is 6.1 times higher per puff than reported previously for conventional cigarette smoke. The detection of a potentially cytotoxic metal as well as oxidants from e-cigarette and its components raises concern regarding the safety of e-cigarettes use and the disposal of e-cigarette waste products into the environment. PMID:25577651

The development of a non-cryogenic nitrogen/oxygen supply system. [using hydrazine/water electrolysis

NASA Technical Reports Server (NTRS)

Greenough, B. M.; Mahan, R. E.

1974-01-01

A hydrazine/water electrolysis process system module design was fabricated and tested to demonstrate component and module performance. This module is capable of providing both the metabolic oxygen for crew needs and the oxygen and nitrogen for spacecraft leak makeup. The component designs evolved through previous R and D efforts, and were fabricated and tested individually and then were assembled into a complete module which was successfully tested for 1000 hours to demonstrate integration of the individual components. A survey was made of hydrazine sensor technology and a cell math model was derived.

Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jablonowski, H.; Hammer, M. U.; Reuter, S.

Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100–400 nm) and, in particular, vacuum ultraviolet (VUV, 10–200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH{sub 2}O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stablemore » reactive oxygen species, hydrogen peroxide (H{sub 2}O{sub 2}) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O{sub 2}{sup •−}) and hydroxyl radicals ({sup •}OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.« less

Sevoflurane protects rat mixed cerebrocortical neuronal-glial cell cultures against transient oxygen-glucose deprivation: involvement of glutamate uptake and reactive oxygen species.

PubMed

Canas, Paula T; Velly, Lionel J; Labrande, Christelle N; Guillet, Benjamin A; Sautou-Miranda, Valérie; Masmejean, Frédérique M; Nieoullon, André L; Gouin, François M; Bruder, Nicolas J; Pisano, Pascale S

2006-11-01

The purpose of this study was to clarify the role of glutamate and reactive oxygen species in sevoflurane-mediated neuroprotection on an in vitro model of ischemia-reoxygenation. Mature mixed cerebrocortical neuronal-glial cell cultures, treated or not with increasing concentrations of sevoflurane, were exposed to 90 min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber followed by reoxygenation. Cell death was quantified by lactate dehydrogenase release into the media and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium by mitochondrial succinate dehydrogenase. Extracellular concentrations of glutamate and glutamate uptake were assessed at the end of the ischemic injury by high-performance liquid chromatography and incorporation of L-[H]glutamate into cells, respectively. Free radical generation in cells was assessed 6 h after OGD during the reoxygenation period using 2',7'-dichlorofluorescin diacetate, which reacts with intracellular radicals to be converted to its fluorescent product, 2',7'-dichlorofluorescin, in cell cytosol. Twenty-four hours after OGD, sevoflurane, in a concentration-dependent manner, significantly reduced lactate dehydrogenase release and increased cell viability. At the end of OGD, sevoflurane was able to reduce the OGD-induced decrease in glutamate uptake. This effect was impaired in the presence of threo-3-methyl glutamate, a specific inhibitor of the glial transporter GLT1. Sevoflurane counteracted the increase in extracellular level of glutamate during OGD and the generation of reactive oxygen species during reoxygenation. Sevoflurane had a neuroprotective effect in this in vitro model of ischemia-reoxygenation. This beneficial effect may be explained, at least in part, by sevoflurane-induced antiexcitotoxic properties during OGD, probably depending on GLT1, and by sevoflurane-induced decrease of reactive oxygen species generation during reoxygenation.

Oxygen concentration inside a functioning photosynthetic cell.

PubMed

Kihara, Shigeharu; Hartzler, Daniel A; Savikhin, Sergei

2014-05-06

The excess oxygen concentration in the photosynthetic membranes of functioning oxygenic photosynthetic cells was estimated using classical diffusion theory combined with experimental data on oxygen production rates of cyanobacterial cells. The excess oxygen concentration within the plesiomorphic cyanobacterium Gloeobactor violaceus is only 0.025 μM, or four orders of magnitude lower than the oxygen concentration in air-saturated water. Such a low concentration suggests that the first oxygenic photosynthetic bacteria in solitary form could have evolved ∼2.8 billion years ago without special mechanisms to protect them against reactive oxygen species. These mechanisms instead could have been developed during the following ∼500 million years while the oxygen level in the Earth's atmosphere was slowly rising. Excess oxygen concentrations within individual cells of the apomorphic cyanobacteria Synechocystis and Synechococcus are 0.064 and 0.25 μM, respectively. These numbers suggest that intramembrane and intracellular proteins in isolated oxygenic photosynthetic cells are not subjected to excessively high oxygen levels. The situation is different for closely packed colonies of photosynthetic cells. Calculations show that the excess concentration within colonies that are ∼40 μm or larger in diameter can be comparable to the oxygen concentration in air-saturated water, suggesting that species forming colonies require protection against reactive oxygen species even in the absence of oxygen in the surrounding atmosphere. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Oxygen Concentration Inside a Functioning Photosynthetic Cell

PubMed Central

Kihara, Shigeharu; Hartzler, Daniel A.; Savikhin, Sergei

2014-01-01

The excess oxygen concentration in the photosynthetic membranes of functioning oxygenic photosynthetic cells was estimated using classical diffusion theory combined with experimental data on oxygen production rates of cyanobacterial cells. The excess oxygen concentration within the plesiomorphic cyanobacterium Gloeobactor violaceus is only 0.025 μM, or four orders of magnitude lower than the oxygen concentration in air-saturated water. Such a low concentration suggests that the first oxygenic photosynthetic bacteria in solitary form could have evolved ∼2.8 billion years ago without special mechanisms to protect them against reactive oxygen species. These mechanisms instead could have been developed during the following ∼500 million years while the oxygen level in the Earth’s atmosphere was slowly rising. Excess oxygen concentrations within individual cells of the apomorphic cyanobacteria Synechocystis and Synechococcus are 0.064 and 0.25 μM, respectively. These numbers suggest that intramembrane and intracellular proteins in isolated oxygenic photosynthetic cells are not subjected to excessively high oxygen levels. The situation is different for closely packed colonies of photosynthetic cells. Calculations show that the excess concentration within colonies that are ∼40 μm or larger in diameter can be comparable to the oxygen concentration in air-saturated water, suggesting that species forming colonies require protection against reactive oxygen species even in the absence of oxygen in the surrounding atmosphere. PMID:24806920

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

PubMed

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

2016-03-02

A novel fusogenic lipidic polyplex (FLPP) vector is designed to fuse with cell membranes, mimicking viropexis, and eject the polyplex into the cytosol, where the cationic polymer is subsequently oxidized by intracellular reactive oxygen species and converts to being negatively charged, efficiently releasing the DNA. The vector delivering suicide gene achieves significantly better inhibition of tumor growth than doxorubicin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Center for Thin Film Studies

DTIC Science & Technology

1988-10-31

techniques, and to investigate the simultaneous use of ion bombardment and substrate cooling for production of low-loss, stable ZnS material. 7 0.14 q(a) N...films indicate that even implanted argon is firmly embedded and shows no tendency to evolve. When the ions are reactive (e.g., oxygen or nitrogen ...oxygen ions can result in very good oxide layers. Nitrogen is another compound-forming gas which lacks sufficient reactivity to have been a useful

HIV-1, Reactive Oxygen Species and Vascular Complications

PubMed Central

Porter, Kristi M.; Sutliff, Roy L.

2012-01-01

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

Reactive Oxygen Species Function to Mediate the Fe Deficiency Response in an Fe-Efficient Apple Genotype: An Early Response Mechanism for Enhancing Reactive Oxygen Production

PubMed Central

Sun, Chaohua; Wu, Ting; Zhai, Longmei; Li, Duyue; Zhang, Xinzhong; Xu, Xuefeng; Ma, Huiqin; Wang, Yi; Han, Zhenhai

2016-01-01

Reactive oxygen species (ROS) are important signaling molecules in plants that contribute to stress acclimation. This study demonstrated that ROS play a critical role in Fe deficiency-induced signaling at an early stage in Malus xiaojinensis. Once ROS production has been initiated, prolonged Fe starvation leads to activation of ROS scavenging mechanisms. Further, we demonstrated that ROS scavengers are involved in maintaining the cellular redox homeostasis during prolonged Fe deficiency treatment. Taken together, our results describe a feedback repression loop for ROS to preserve redox homeostasis and maintain a continuous Fe deficiency response in the Fe-efficient woody plant M. xiaojinensis. More broadly, this study reveals a new mechanism in which ROS mediate both positive and negative regulation of plant responses to Fe deficiency stress. PMID:27899933

Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise.

PubMed

Thirupathi, Anand; de Souza, Claudio Teodoro

2017-11-01

Transcriptional factors are easily susceptible to any stimuli, including exercise. Exercise can significantly influence PGC-1 α and AMPK-SIRT1 pathway, as it is involved in the regulation of energy metabolism and mitochondrial biogenesis. Exercise is a major energy deprivation process by which many of transcription factors get tuned positively. However, how transcription factors help to boost the antioxidant defense system at cellular level is elusive. It is well known that physical exercise can induce reactive oxygen species, but how these reactive oxygen species can help to regulate multiple transcription factors during exercise is an important area to be discussed yet. This review mainly focuses on interconnecting role of PGC-1 α and AMPK-SIRT1 pathway during exercise and how these proteins are getting tuned by reactive oxygen species in exercise condition.

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

NASA Astrophysics Data System (ADS)

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

The partial pressure of oxygen affects biomarkers of oxidative stress in cultured rainbow trout (Oncorhynchus mykiss) hepatocytes.

PubMed

Finne, E F; Olsvik, P A; Berntssen, M H G; Hylland, K; Tollefsen, K E

2008-09-01

Oxidative stress, the imbalance between production of reactive oxygen species and the cellular detoxification of these reactive compounds, is believed to be involved in the pathology of various diseases. Several biomarkers for oxidative stress have been proposed to serve as tools in toxicological and ecotoxicological research. Not only may exposure to various pro-oxidants create conditions of cellular oxidative stress, but hyperoxic conditions may also increase the production of reactive oxygen species. The objective of the current study was to determine the extent to which differences in oxygen partial pressure would affect biomarkers of oxidative stress in a primary culture of hepatocytes from rainbow trout (Oncorhynchus mykiss). Membrane integrity, metabolic activity, levels of total and oxidized glutathione (tGSH/GSSG) was determined, as well as mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), gamma-glutamyl-cystein synthetase (GCS) and thioredoxin (TRX). The results show that different biomarkers of oxidative stress are affected when the cell culture is exposed to atmospheric oxygen, and that changes such as increased GSSG content and induction of GSSG-R and GSH-Px can be reduced by culturing the cells under lower oxygen tension. Oxygen tension may thus influence results of in vitro based cell research and is particularly important when assessing parameters in the antioxidant defence system. Further research is needed to establish the magnitude of this effect in different cellular systems.

Enhancing surface functionality of reduced graphene oxide biosensors by oxygen plasma treatment for Alzheimer's disease diagnosis.

PubMed

Chae, Myung-Sic; Kim, Jinsik; Jeong, Dahye; Kim, YoungSoo; Roh, Jee Hoon; Lee, Sung Min; Heo, Youhee; Kang, Ji Yoon; Lee, Jeong Hoon; Yoon, Dae Sung; Kim, Tae Geun; Chang, Suk Tai; Hwang, Kyo Seon

2017-06-15

We performed oxygen plasma treatment on reduced graphene oxide (rGO) to improve its surface reactivity with respect to biomolecular interactions. Oxygen-plasma-treated rGO surfaces were employed as reactive interfaces for the detection of amyloid-beta (Aβ) peptides, the pathological hallmarks of Alzheimer's disease (AD), as the target analytes. By measuring the changes in electrical characteristics and confirmation through topographic analysis, the oxygen-plasma-treated rGO sensors had enhanced surface functionality for better antibody immobilization and sensing performance, with a 3.33-fold steeper slope for the electrical responses versus analyte concentration curve (logarithmic scale) compared to the untreated. The elicited biomolecular reactivity of the rGO surfaces with the oxygen plasma treatment remained at 46-51% of the initial value even after aging for 6h in ambient conditions. This phenomenon was also confirmed by pretreating the rGO surfaces with a blocking agent and subsequently subjecting them to antibody immobilization. Finally, the feasibility of the oxygen-plasma-treated rGO sensors as a diagnostic tool was evaluated with clinical samples of neural-derived exosomal Aβ peptides extracted from apparent AD patients and normal controls (NC). In contrast to the untreated sensors (p=0.0460), the oxygen-plasma-treated rGO sensors showed a significant p-value in the identification of clinical samples of AD and NC subjects (p<0.001). These results suggest that oxygen plasma treatment improves sensor performance without complicated fabrication procedures and should aid in the development of novel diagnostic tools based on carbon nanomaterials. Copyright © 2016 Elsevier B.V. All rights reserved.

Relation of Mitochondrial Oxygen Consumption in Peripheral Blood Mononuclear Cells to Vascular Function in Type 2 Diabetes Mellitus

PubMed Central

Hartman, Mor-Li; Shirihai, Orian S.; Holbrook, Monika; Xu, Guoquan; Kocherla, Marsha; Shah, Akash; Fetterman, Jessica L.; Kluge, Matthew A.; Frame, Alissa A.; Hamburg, Naomi M.; Vita, Joseph A.

2014-01-01

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMC’s) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to ATP production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMC’s that would correlate with endothelial dysfunction. We developed a method to measure oxygen consumption in freshly isolated PBMC’s and applied it to 26 patients with type 2 diabetes mellitus and 28 non-diabetic controls. Basal (192±47 vs. 161±44 pMoles/min, P=0.01), uncoupled (64±16 vs. 53±16 pMoles/min, P=0.007), and maximal (795±87 vs. 715±128 pMoles/min, P=0.01) oxygen consumption rates were higher in diabetic patients compared to controls. There were no significant correlations between oxygen consumption rates and endothelium-dependent flow-mediated dilation measured by vascular ultrasound. Non-endothelium-dependent nitroglycerin-mediated dilation was lower in diabetics (10.1±6.6 vs. 15.8±4.8%, P=0.03) and correlated with maximal oxygen consumption (R= −0.64, P=0.001). In summary, we found that diabetes mellitus is associated with a pattern of mitochondrial oxygen consumption consistent with higher production of reactive oxygen species. The correlation between oxygen consumption and nitroglycerin-mediated dilation may suggest a link between mitochondrial dysfunction and vascular smooth muscle cell dysfunction that merits further study. Finally, the described method may have utility for assessment of mitochondrial function in larger scale observational and interventional studies in humans. PMID:24558030

Single-cell, real-time detection of oxidative stress induced in Escherichia coli by the antimicrobial peptide CM15.

PubMed

Choi, Heejun; Yang, Zhilin; Weisshaar, James C

2015-01-20

Antibiotics target specific biochemical mechanisms in bacteria. In response to new drugs, pathogenic bacteria rapidly develop resistance. In contrast, antimicrobial peptides (AMPs) have retained broad spectrum antibacterial potency over millions of years. We present single-cell fluorescence assays that detect reactive oxygen species (ROS) in the Escherichia coli cytoplasm in real time. Within 30 s of permeabilization of the cytoplasmic membrane by the cationic AMP CM15 [combining residues 1-7 of cecropin A (from moth) with residues 2-9 of melittin (bee venom)], three fluorescence signals report oxidative stress in the cytoplasm, apparently involving O2 (-), H2O2, and •OH. Mechanistic studies indicate that active respiration is a prerequisite to the CM15-induced oxidative damage. In anaerobic conditions, signals from ROS are greatly diminished and the minimum inhibitory concentration increases 20-fold. Evidently the natural human AMP LL-37 also induces a burst of ROS. Oxidative stress may prove a significant bacteriostatic mechanism for a variety of cationic AMPs. If so, host organisms may use the local oxygen level to modulate AMP potency.

Differential roles of NADPH oxidases in vascular physiology and pathophysiology

PubMed Central

Amanso, Angelica M.; Griendling, Kathy K.

2012-01-01

Reactive oxygen species (ROS) are produced by all vascular cells and regulate the major physiological functions of the vasculature. Production and removal of ROS are tightly controlled and occur in discrete subcellular locations, allowing for specific, compartmentalized signaling. Among the many sources of ROS in the vessel wall, NADPH oxidases are implicated in physiological functions such as control of vasomotor tone, regulation of extracellular matrix and phenotypic modulation of vascular smooth muscle cells. They are involved in the response to injury, whether as an oxygen sensor during hypoxia, as a regulator of protein processing, as an angiogenic stimulus, or as a mechanism of wound healing. These enzymes have also been linked to processes leading to disease development, including migration, proliferation, hypertrophy, apoptosis and autophagy. As a result, NADPH oxidases participate in atherogenesis, systemic and pulmonary hypertension and diabetic vascular disease. The role of ROS in each of these processes and diseases is complex, and a more full understanding of the sources, targets, cell-specific responses and counterbalancing mechanisms is critical for the rational development of future therapeutics. PMID:22202108

Functions of tocopherols in the cells of plants and other photosynthetic organisms.

PubMed

Mokrosnop, V M

2014-01-01

Tocopherol synthesis has only been observed in photosynthetic organisms (plants, algae and some cyanobacteria). Tocopherol is synthesized in the inner membrane of chloroplasts and distributed between chloroplast membranes, thylakoids and plastoglobules. Physiological significance of tocopherols for human and animal is well-studied, but relatively little is known about their function in plant organisms. Among the best characterized functions oftocopherols in cells is their ability to scavenge and quench reactive oxygen species and fat-soluble by-products of oxidative stress. There are the data on the participation of different mechanisms of α-tocopherol action in protecting photosystem II (PS II) from photoinhibition both by deactivation of singlet oxygen produced by PSII and by reduction of proton permeability of thylakoid membranes, leading to acidification of lumen under high light conditions and activation of violaxanthin de-epoxidase. Additional biological activity of tocopherols, independent of its antioxidant functions have been demonstrated. Basic mechanisms for these effects are connected with the modulation of signal transduction pathways by specific tocopherols and, in some instances, by transcriptional activation of gene expression.

Nitric oxide plays a role in stem cell niche homeostasis through its interaction with auxin.

PubMed

Sanz, Luis; Fernández-Marcos, María; Modrego, Abelardo; Lewis, Daniel R; Muday, Gloria K; Pollmann, Stephan; Dueñas, Montserrat; Santos-Buelga, Celestino; Lorenzo, Oscar

2014-12-01

Nitric oxide (NO) is a unique reactive nitrogen molecule with an array of signaling functions that modulates plant developmental processes and stress responses. To explore the mechanisms by which NO modulates root development, we used a pharmacological approach and NO-deficient mutants to unravel the role of NO in establishing auxin distribution patterns necessary for stem cell niche homeostasis. Using the NO synthase inhibitor and Arabidopsis (Arabidopsis thaliana) NO biosynthesis mutants (nitric oxide-associated1 [noa1], nitrate reductase1 [nia1] and nia2, and nia1 nia2 noa1), we show that depletion of NO in noa1 reduces primary root elongation and increases flavonol accumulation consistent with elevated reactive oxygen species levels. The elevated flavonols are required for the growth effect, because the transparent testa4 mutation reverses the noa1 mutant root elongation phenotype. In addition, noa1 and nia1 nia2 noa1 NO-deficient mutant roots display small root meristems with abnormal divisions. Concomitantly, auxin biosynthesis, transport, and signaling are perturbed. We further show that NO accumulates in cortex/endodermis stem cells and their precursor cells. In endodermal and cortical cells, the noa1 mutant acts synergistically to the effect of the wuschel-related homeobox5 mutation on the proximal meristem, suggesting that NO could play an important role in regulating stem cell decisions, which has been reported in animals. © 2014 American Society of Plant Biologists. All Rights Reserved.

Continuum-based DFN-consistent numerical framework for the simulation of oxygen infiltration into fractured crystalline rocks.

PubMed

Trinchero, Paolo; Puigdomenech, Ignasi; Molinero, Jorge; Ebrahimi, Hedieh; Gylling, Björn; Svensson, Urban; Bosbach, Dirk; Deissmann, Guido

2017-05-01

We present an enhanced continuum-based approach for the modelling of groundwater flow coupled with reactive transport in crystalline fractured rocks. In the proposed formulation, flow, transport and geochemical parameters are represented onto a numerical grid using Discrete Fracture Network (DFN) derived parameters. The geochemical reactions are further constrained by field observations of mineral distribution. To illustrate how the approach can be used to include physical and geochemical complexities into reactive transport calculations, we have analysed the potential ingress of oxygenated glacial-meltwater in a heterogeneous fractured rock using the Forsmark site (Sweden) as an example. The results of high-performance reactive transport calculations show that, after a quick oxygen penetration, steady state conditions are attained where abiotic reactions (i.e. the dissolution of chlorite and the homogeneous oxidation of aqueous iron(II) ions) counterbalance advective oxygen fluxes. The results show that most of the chlorite becomes depleted in the highly conductive deformation zones where higher mineral surface areas are available for reactions. Copyright © 2017 Elsevier B.V. All rights reserved.

Control mechanisms in mitochondrial oxidative phosphorylation☆

PubMed Central

Hroudová, Jana; Fišar, Zdeněk

2013-01-01

Distribution and activity of mitochondria are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5’- triphosphate production is regulated by many control mechanism–firstly by oxygen, substrate level, adenosine-5’-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by “second control mechanisms,” such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, allosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5’-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria, similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production. PMID:25206677

Control mechanisms in mitochondrial oxidative phosphorylation.

PubMed

Hroudová, Jana; Fišar, Zdeněk

2013-02-05

Distribution and activity of mitochondria are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5'- triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by "second control mechanisms," such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, allosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5'-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria, similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.

Reactive oxygen species explicit dosimetry (ROSED) of a type 1 photosensitizer

NASA Astrophysics Data System (ADS)

Ong, Yi Hong; Kim, Michele M.; Huang, Zheng; Zhu, Timothy C.

2018-02-01

Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging

PubMed Central

Carpenter, C. M.; Rakow-Penner, R.; Jiang, S.; Pogue, B. W.; Glover, G. H.; Paulsen, K. D.

2010-01-01

Purpose: The modulation of tissue hemodynamics has important clinical value in medicine for both tumor diagnosis and therapy. As an oncological tool, increasing tissue oxygenation via modulation of inspired gas has been proposed as a method to improve cancer therapy and determine radiation sensitivity. As a radiological tool, inducing changes in tissue total hemoglobin may provide a means to detect and characterize malignant tumors by providing information about tissue vascular function. The ability to change and measure tissue hemoglobin and oxygenation concentrations in the healthy breast during administration of three different types of modulated gas stimuli (oxygen∕carbogen, air∕carbogen, and air∕oxygen) was investigated. Methods: Subjects breathed combinations of gases which were modulated in time. MR-guided diffuse optical tomography measured total hemoglobin and oxygen saturation in the breast every 30 s during the 16 min breathing stimulus. Metrics of maximum correlation and phase lag were calculated by cross correlating the measured hemodynamics with the stimulus. These results were compared to an air∕air control to determine the hemodynamic changes compared to the baseline physiology. Results: This study demonstrated that a gas stimulus consisting of alternating oxygen∕carbogen induced the largest and most robust hemodynamic response in healthy breast parenchyma relative to the changes that occurred during the breathing of room air. This stimulus caused increases in total hemoglobin and oxygen saturation during the carbogen phase of gas inhalation, and decreases during the oxygen phase. These findings are consistent with the theory that oxygen acts as a vasoconstrictor, while carbogen acts as a vasodilator. However, difficulties in inducing a consistent change in tissue hemoglobin and oxygenation were observed because of variability in intersubject physiology, especially during the air∕oxygen or air∕carbogen modulated breathing protocols. Conclusions: MR-guided diffuse optical imaging is a unique tool that can measure tissue hemodynamics in the breast during modulated breathing. This technique may have utility in determining the therapeutic potential of pretreatment tissue oxygenation or in investigating vascular function. Future gas modulation studies in the breast should use a combination of oxygen and carbogen as the functional stimulus. Additionally, control measures of subject physiology during air breathing are critical for robust measurements. PMID:20443485

Module for Oxygenating Water without Generating Bubbles

NASA Technical Reports Server (NTRS)

Gonzalez-Martin, Anuncia; Sidik, Reyimjan; Kim, Jinseong

2004-01-01

A module that dissolves oxygen in water at concentrations approaching saturation, without generating bubbles of oxygen gas, has been developed as a prototype of improved oxygenators for water-disinfection and water-purification systems that utilize photocatalyzed redox reactions. Depending on the specific nature of a water-treatment system, it is desirable to prevent the formation of bubbles for one or more reasons: (1) Bubbles can remove some organic contaminants from the liquid phase to the gas phase, thereby introducing a gas-treatment problem that complicates the overall water-treatment problem; and/or (2) in some systems (e.g., those that must function in microgravity or in any orientation in normal Earth gravity), bubbles can interfere with the flow of the liquid phase. The present oxygenation module (see Figure 1) is a modified version of a commercial module that contains >100 hollow polypropylene fibers with a nominal pore size of 0.05 m and a total surface area of 0.5 m2. The module was originally designed for oxygenation in a bioreactor, with no water flowing around or inside the tubes. The modification, made to enable the use of the module to oxygenate flowing water, consisted mainly in the encapsulation of the fibers in a tube of Tygon polyvinyl chloride (PVC) with an inside diameter of 1 in. (approx.=25 mm). In operation, water is pumped along the insides of the hollow fibers and oxygen gas is supplied to the space outside the hollow tubes inside the PVC tube. In tests, the pressure drops of water and oxygen in the module were found to be close to zero at water-flow rates ranging up to 320 mL/min and oxygen-flow rates up to 27 mL/min. Under all test conditions, no bubbles were observed at the water outlet. In some tests, flow rates were chosen to obtain dissolved-oxygen concentrations between 25 and 31 parts per million (ppm) . approaching the saturation level of approx.=35 ppm at a temperature of 20 C and pressure of 1 atm (approx.=0.1 MPa). As one would expect, it was observed that the time needed to bring a flow of water from an initial low dissolved-oxygen concentration (e.g., 5 ppm) to a steady high dissolved-oxygen concentration at or near the saturation level depends on the rates of flow of both oxygen and water, among other things. Figure 2 shows the results of an experiment in which a greater flow of oxygen was used during the first few tens of minutes to bring the concentration up to approx.=25 ppm, then a lesser flow was used to maintain the concentration.

A Conformational Change in C-Reactive Protein Enhances Leukocyte Recruitment and Reactive Oxygen Species Generation in Ischemia/Reperfusion Injury.

PubMed

Thiele, Jan R; Zeller, Johannes; Kiefer, Jurij; Braig, David; Kreuzaler, Sheena; Lenz, Yvonne; Potempa, Lawrence A; Grahammer, Florian; Huber, Tobias B; Huber-Lang, M; Bannasch, Holger; Stark, G Björn; Peter, Karlheinz; Eisenhardt, Steffen U

2018-01-01

C-reactive protein circulates as a pentameric protein (pCRP). pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isoforms expressing pro-inflammatory neo-epitopes [pCRP* and monomeric C-reactive protein (mCRP)]. Here, we investigate the role of CRP isoforms in renal ischemia/reperfusion injury (IRI). Rat kidneys in animals with and without intraperitoneally injected pCRP were subjected to IRI by the time of pCRP exposure and were subsequently analyzed for monocyte infiltration, caspase-3 expression, and tubular damage. Blood urea nitrogen (BUN) was analyzed pre-ischemia and post-reperfusion. CRP effects on leukocyte recruitment were investigated via intravital imaging of rat-striated muscle IRI. Localized conformational CRP changes were analyzed by immunohistochemistry using conformation specific antibodies. 1,6-bis(phosphocholine)-hexane (1,6-bisPC), which stabilizes CRP in its native pentameric form was used to validate CRP effects. Leukocyte activation was assessed by quantification of reactive oxygen species (ROS) induction by CRP isoforms ex vivo and in vitro through electron spin resonance spectroscopy. Signaling pathways were analyzed by disrupting lipid rafts with nystatin and subsequent ROS detection. In order to confirm the translational relevance of our findings, biopsies of microsurgical human free tissue transfers before and after IRI were examined by immunofluorescence for CRP deposition and co-localization of CD68 + leukocytes. The application of pCRP aggravates tissue damage in renal IRI. 1,6-bisPC reverses these effects via inhibition of the conformational change that leads to exposure of pro-inflammatory epitopes in CRP (pCRP* and mCRP). Structurally altered CRP induces leukocyte-endothelial interaction and induces ROS formation in leukocytes, the latter can be abrogated by blocking lipid raft-dependent signaling pathways with Nystatin. Stabilizing pCRP in its native pentameric state abrogates these pro-inflammatory effects. Importantly, these findings are confirmed in human IRI challenged muscle tissue. These results suggest that CRP is a potent modulator of IRI. Stabilizing the native pCRP conformation represents a promising anti-inflammatory therapeutic strategy by attenuation of leukocyte recruitment and ROS formation, the primary pathomechanisms of IRI.

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anders, André

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. Furthermore, by applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films.more » Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become “poisoned,” i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.« less

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

DOE PAGES

Anders, André

2017-03-21

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. Furthermore, by applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films.more » Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become “poisoned,” i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.« less

Tutorial: Reactive high power impulse magnetron sputtering (R-HiPIMS)

NASA Astrophysics Data System (ADS)

Anders, André

2017-05-01

High Power Impulse Magnetron Sputtering (HiPIMS) is a coating technology that combines magnetron sputtering with pulsed power concepts. By applying power in pulses of high amplitude and a relatively low duty cycle, large fractions of sputtered atoms and near-target gases are ionized. In contrast to conventional magnetron sputtering, HiPIMS is characterized by self-sputtering or repeated gas recycling for high and low sputter yield materials, respectively, and both for most intermediate materials. The dense plasma in front of the target has the dual function of sustaining the discharge and providing plasma-assistance to film growth, affecting the microstructure of growing films. Many technologically interesting thin films are compound films, which are composed of one or more metals and a reactive gas, most often oxygen or nitrogen. When reactive gas is added, non-trivial consequences arise for the system because the target may become "poisoned," i.e., a compound layer forms on the target surface affecting the sputtering yield and the yield of secondary electron emission and thereby all other parameters. It is emphasized that the target state depends not only on the reactive gas' partial pressure (balanced via gas flow and pumping) but also on the ion flux to the target, which can be controlled by pulse parameters. This is a critical technological opportunity for reactive HiPIMS (R-HiPIMS). The scope of this tutorial is focused on plasma processes and mechanisms of operation and only briefly touches upon film properties. It introduces R-HiPIMS in a systematic, step-by-step approach by covering sputtering, magnetron sputtering, reactive magnetron sputtering, pulsed reactive magnetron sputtering, HiPIMS, and finally R-HiPIMS. The tutorial is concluded by considering variations of R-HiPIMS known as modulated pulsed power magnetron sputtering and deep-oscillation magnetron sputtering and combinations of R-HiPIMS with superimposed dc magnetron sputtering.

Fluorinated methacrylamide chitosan sequesters reactive oxygen species to relieve oxidative stress while delivering oxygen.

PubMed

Patil, Pritam S; Leipzig, Nic D

2017-08-01

Antioxidants play an important role in regulating overabundant reactive oxygen species (ROS) in wound healing to reduce oxidative stress and inflammation. In this work, we demonstrate for the first time that functionalization of methacrylamide chitosan (MAC) with aliphatic pentadecafluoro chains, to synthesize pentadecafluoro-octanoyl methacrylamide chitosan (MACF), enhances the antioxidant capacity of the MAC base hydrogel material, while being able to deliver oxygen for future enhanced wound healing applications. As such, MACF was shown to sequester more nitric oxide (p < 0.01) and hydroxyl (p < 0.0001) radicals as compared to the negative control even when delivering additional oxygen. MACF's beneficial antioxidant capacity was further confirmed in in vitro cell culture experiments using human dermal fibroblasts stressed with 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2368-2374, 2017. © 2017 Wiley Periodicals, Inc.

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

NASA Technical Reports Server (NTRS)

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

1998-01-01

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

First kinetic discrimination between carbon and oxygen reactivity of enols.

PubMed

García-Río, Luis; Mejuto, Juan C; Parajó, Mercedes; Pérez-Lorenzo, Moisés

2008-11-07

Nitrosation of enols shows a well-differentiated behavior depending on whether the reaction proceeds through the carbon (nucleophilic catalysis is observed) or the oxygen atom (general acid-base catalysis is observed). This is due to the different operating mechanisms for C- and O-nitrosation. Nitrosation of acetylacetone (AcAc) shows a simultaneous nucleophilic and acid-base catalysis. This simultaneous catalysis constitutes the first kinetic evidence of two independent reactions on the carbon and oxygen atom of an enol. The following kinetic study allows us to determine the rate constants for both reaction pathways. A similar reactivity of the nucleophilic centers with the nitrosonium ion is observed.

Plasma reactivity in high-power impulse magnetron sputtering through oxygen kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vitelaru, Catalin; National Institute for Optoelectronics, Magurele-Bucharest, RO 077125; Lundin, Daniel

2013-09-02

The atomic oxygen metastable dynamics in a Reactive High-Power Impulse Magnetron Sputtering (R-HiPIMS) discharge has been characterized using time-resolved diode laser absorption in an Ar/O{sub 2} gas mixture with a Ti target. Two plasma regions are identified: the ionization region (IR) close to the target and further out the diffusion region (DR), separated by a transition region. The μs temporal resolution allows identifying the main atomic oxygen production and destruction routes, which are found to be very different during the pulse as compared to the afterglow as deduced from their evolution in space and time.

Benzoylation of Ergosterol through Nucleophilic Acyl Substitution and Subsequent Formation of Ergosterol Benzoate Endoperoxide by Reaction with Singlet Oxygen Generated by Photosensitization

ERIC Educational Resources Information Center

Roslaniec, Mary C.; Sanford, Elizabeth M.

2011-01-01

Reactive oxygen species such as singlet oxygen have been a major focus of research in medicine. The effect of singlet oxygen on sterols within biological membranes is becoming increasingly more important. Ergosterol, a vitamin D precursor, is one such sterol. The benzoylation of ergosterol and subsequent reaction with singlet oxygen to form an…

Model based verification and prognosis of acidification and sulphate releasing processes downstream of a former sewage field in Berlin (Germany).

PubMed

Horner, Christoph; Engelmann, Frank; Nützmann, Gunnar

2009-04-15

An ammonium contamination plume originating from sewage field management practices over several decades is affecting the water quality at the well fields of the Friedrichshagen waterworks in Berlin, Germany. Because hydraulic measures were unsuccessful due to the fixation of ammonium on the aquifer matrix by cation exchange, an in situ nitrification measure by injection of oxygen gas was chosen to protect the extraction wells. In order to assess the hydro chemical processes accompanying this in situ measure, reactive transport modelling was performed. The relevant processes are the dissolution of oxygen gas and the nitrification of ammonium which initiate secondary geochemical processes like sulphate release, acidification and hardening. The reactive transport modelling began with the deduction of a reaction network, followed by the mathematical formulation and incorporation of reactive terms into a reactive transport solver. Two model versions were set up: (1) a simplified large scale model to evaluate the long-term reaction zoning to be expected due to permanent oxygen gas injection, and (2) a verification of the monitored hydrochemistry during a first field test performed near the contamination source. The results of reactive transport modelling demonstrate that in situ injection of oxygen gas will be effective in reducing the ammonium load from the well fields, and that acidification processes near the production wells can be minimized. Finally, a line of gas injection wells extending over the whole width of the ammonium contamination plume will be constructed to protect the well fields from further ammonium load.

Characterization and reactivity of a terminal nickel(III)-oxygen adduct.

PubMed

Pirovano, Paolo; Farquhar, Erik R; Swart, Marcel; Fitzpatrick, Anthony J; Morgan, Grace G; McDonald, Aidan R

2015-02-23

High-valent terminal metal-oxygen adducts are hypothesized to be the potent oxidizing reactants in late transition metal oxidation catalysis. In particular, examples of high-valent terminal nickel-oxygen adducts are scarce, meaning there is a dearth in the understanding of such oxidants. A monoanionic Ni(II)-bicarbonate complex has been found to react in a 1:1 ratio with the one-electron oxidant tris(4-bromophenyl)ammoniumyl hexachloroantimonate, yielding a thermally unstable intermediate in high yield (ca. 95%). Electronic absorption, electronic paramagnetic resonance, and X-ray absorption spectroscopies and density functional theory calculations confirm its description as a low-spin (S = 1/2), square planar Ni(III)-oxygen adduct. This rare example of a high-valent terminal nickel-oxygen complex performs oxidations of organic substrates, including 2,6-di-tert-butylphenol and triphenylphosphine, which are indicative of hydrogen atom abstraction and oxygen atom transfer reactivity, respectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"Dark" Singlet Oxygen and Electron Paramagnetic Resonance Spin Trapping as Convenient Tools to Assess Photolytic Drug Degradation.

PubMed

Persich, Peter; Hostyn, Steven; Joie, Céline; Winderickx, Guy; Pikkemaat, Jeroen; Romijn, Edwin P; Maes, Bert U W

2017-05-01

Forced degradation studies are an important tool for a systematic assessment of decomposition pathways and identification of reactive sites in active pharmaceutical ingredients (APIs). Two methodologies have been combined in order to provide a deeper understanding of singlet oxygen-related degradation pathways of APIs under light irradiation. First, we report that a "dark" singlet oxygen test enables the investigation of drug reactivity toward singlet oxygen independently of photolytic irradiation processes. Second, the photosensitizing properties of the API producing the singlet oxygen was proven and quantified by spin trapping and electron paramagnetic resonance analysis. A combination of these techniques is an interesting addition to the forced degradation portfolio as it can be used for (1) revealing unexpected degradation pathways of APIs due to singlet oxygen, (2) clarifying photolytic drug-drug interactions in fixed-dose combinations, and (3) synthesizing larger quantities of hardly accessible oxidative drug degradants. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Enhancing Dissociative Adsorption of Water on Cu(111) via Chemisorbed Oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qianqian; Li, Jonathan; Tong, Xiao

We have used X-ray photoelectron spectroscopy to study the dehydrogenation of H 2O molecules on the clean and oxygenated Cu(111) surfaces. The clean surface does not show reactivity toward H 2O dehydrogenation. By contrast, H 2O molecules on the oxygenated Cu(111) dissociate into OH species by reacting with chemisorbed oxygen until the complete consumption of the chemisorbed oxygen at which the surface loses its reactivity toward H 2O dehydrogenation. Increasing the temperature to 200 °C and above decreases molecularly adsorbed H 2O for dehydrogenation, thereby resulting in less loss of chemisorbed O. In conjunction with density-functional theory calculations, a three-stepmore » reaction pathway is proposed to account for the chemisorbed O assisted dehydrogenation of H 2O molecules and the net loss of surface oxygen. Finally, these results provide insight into understanding the elemental steps of the dehydrogenation of H 2O molecules and the controllable conditions for tuning H 2O dissociation on metal surfaces.« less

Enhancing Dissociative Adsorption of Water on Cu(111) via Chemisorbed Oxygen

DOE PAGES

Liu, Qianqian; Li, Jonathan; Tong, Xiao; ...

2017-05-16

We have used X-ray photoelectron spectroscopy to study the dehydrogenation of H 2O molecules on the clean and oxygenated Cu(111) surfaces. The clean surface does not show reactivity toward H 2O dehydrogenation. By contrast, H 2O molecules on the oxygenated Cu(111) dissociate into OH species by reacting with chemisorbed oxygen until the complete consumption of the chemisorbed oxygen at which the surface loses its reactivity toward H 2O dehydrogenation. Increasing the temperature to 200 °C and above decreases molecularly adsorbed H 2O for dehydrogenation, thereby resulting in less loss of chemisorbed O. In conjunction with density-functional theory calculations, a three-stepmore » reaction pathway is proposed to account for the chemisorbed O assisted dehydrogenation of H 2O molecules and the net loss of surface oxygen. Finally, these results provide insight into understanding the elemental steps of the dehydrogenation of H 2O molecules and the controllable conditions for tuning H 2O dissociation on metal surfaces.« less

Measurements of volatile organic compounds during the 2006 TexAQS/GoMACCS campaign: Industrial influences, regional characteristics, and diurnal dependencies of the OH reactivity

NASA Astrophysics Data System (ADS)

Gilman, Jessica B.; Kuster, William C.; Goldan, Paul D.; Herndon, Scott C.; Zahniser, Mark S.; Tucker, Sara C.; Brewer, W. Alan; Lerner, Brian M.; Williams, Eric J.; Harley, Robert A.; Fehsenfeld, Fred C.; Warneke, Carsten; de Gouw, Joost A.

2009-04-01

An extensive set of volatile organic compounds (VOCs) and other gas phase species were measured in situ aboard the NOAA R/V Ronald H. Brown as the ship sailed in the Gulf of Mexico and the Houston and Galveston Bay (HGB) area as part of the Texas Air Quality (TexAQS)/Gulf of Mexico Atmospheric Composition and Climate Study (GoMACCS) conducted from July-September 2006. The magnitudes of the reactivities of CH4, CO, VOCs, and NO2 with the hydroxyl radical, OH, were determined in order to quantify the contributions of these compounds to potential ozone formation. The average total OH reactivity (ROH,TOTAL) increased from 1.01 s-1 in the central gulf to 10.1 s-1 in the HGB area as a result of the substantial increase in the contribution from VOCs and NO2. The increase in the measured concentrations of reactive VOCs in the HGB area compared to the central gulf was explained by the impact of industrial emissions, the regional distribution of VOCs, and the effects of local meteorology. By compensating for the effects of boundary layer mixing, the diurnal profiles of the OH reactivity were used to characterize the source signatures and relative magnitudes of biogenic, anthropogenic (urban + industrial), and oxygenated VOCs as a function of the time of day. The source of reactive oxygenated VOCs (e.g., formaldehyde) was determined to be almost entirely from secondary production. The secondary formation of oxygenated VOCs, in addition to the continued emissions of reactive anthropogenic VOCs, served to sustain elevated levels of OH reactivity throughout the time of peak ozone production.

Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4.

PubMed

Olthof, Evelyn D; Gülich, Alexandra F; Renne, Mike F; Landman, Sija; Joosten, Leo A B; Roelofs, Hennie M J; Wanten, Geert J A

2015-10-01

Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO. To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n-3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production. All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT-induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT-induced changes in immune function. Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

The aryl hydrocarbon receptor modulates acute and late mast cell responses.

PubMed

Sibilano, Riccardo; Frossi, Barbara; Calvaruso, Marco; Danelli, Luca; Betto, Elena; Dall'Agnese, Alessandra; Tripodo, Claudio; Colombo, Mario P; Pucillo, Carlo E; Gri, Giorgia

2012-07-01

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.

Impact of carbon, oxygen and sulfur content of microscale zerovalent iron particles on its reactivity towards chlorinated aliphatic hydrocarbons.

PubMed

Velimirovic, Milica; Larsson, Per-Olof; Simons, Queenie; Bastiaens, Leen

2013-11-01

Zerovalent iron (ZVI) abiotically degrades several chlorinated aliphatic hydrocarbons (CAHs) via reductive dechlorination, which offers perspectives for in situ groundwater remediation applications. The difference in reactivity between ZVI particles is often linked with their specific surface area. However, other parameters may influence the reactivity as well. Earlier, we reported for a set of microscale zerovalent iron (mZVI) particles the disappearance kinetic of different CAHs which were collected under consistent experimental conditions. In the present study, these kinetic data were correlated with the carbon, oxygen and sulfur content of mZVI particles. It was confirmed that not only the specific surface area affects the disappearance kinetic of CAHs, but also the chemical composition of the mZVI particles. The chemical composition, in addition, influences CAHs removal mechanism inducing sorption onto mZVI particles instead of dechlorination. Generally, high disappearance kinetic of CAHs was observed for particles containing less oxygen. A high carbon content, on the other hand, induced nonreactive sorption of the contaminants on the mZVI particles. To obtain efficient remediation of CAHs by mZVI particles, this study suggested that the carbon and oxygen content should not exceed 0.5% and 1% respectively. Finally, the efficiency of the mZVI particles may be improved to some extent by enriching them with sulfur. However, the impact of sulfur content on the reactivity of mZVI particles is less pronounced than that of the carbon and oxygen content. Copyright © 2013 Elsevier Ltd. All rights reserved.

Generation of reactive oxygen species and charge carriers in plasmonic photocatalytic Au@TiO2 nanostructures with enhanced activity.

PubMed

He, Weiwei; Cai, Junhui; Jiang, Xiumei; Yin, Jun-Jie; Meng, Qingbo

2018-06-13

The combination of semiconductor and plasmonic nanostructures, endowed with high efficiency light harvesting and surface plasmon confinement, has been a promising way for efficient utilization of solar energy. Although the surface plasmon resonance (SPR) assisted photocatalysis has been extensively studied, the photochemical mechanism, e.g. the effect of SPR on the generation of reactive oxygen species and charge carriers, is not well understood. In this study, we take Au@TiO2 nanostructures as a plasmonic photocatalyst to address this critical issue. The Au@TiO2 core/shell nanostructures with tunable SPR property were synthesized by the templating method with post annealing thermal treatment. It was found that Au@TiO2 nanostructures exhibit enhanced photocatalytic activity in either sunlight or visible light (λ > 420 nm). Electron spin resonance spectroscopy with spin trapping and spin labeling was used to investigate the enhancing effect of Au@TiO2 on the photo-induced reactive oxygen species and charge carriers. The formation of Au@TiO2 core/shell nanostructures resulted in a dramatic increase in light-induced generation of hydroxyl radicals, singlet oxygen, holes and electrons, as compared with TiO2 alone. This enhancement under visible light (λ > 420 nm) irradiation may be dominated by SPR induced local electrical field enhancement, while the enhancement under sunlight irradiation is dominated by the higher electron transfer from TiO2 to Au. These results unveiled that the superior photocatalytic activity of Au@TiO2 nanostructures correlates with enhanced generation of reactive oxygen species and charge carriers.

Unusual Reactivity of the Martian Soil: Oxygen Release Upon Humidification

NASA Technical Reports Server (NTRS)

Yen, A. S.

2002-01-01

Recent lab results show that oxygen evolves from superoxide-coated mineral grains upon exposure to water vapor. This observation is additional support of the hypothesis that UV-generated O2 is responsible for the reactivity of the martian soil. Discussion of current NASA research opportunities, status of various programs within the Solar System Exploration Division, and employment opportunities within NASA Headquarters to support these programs. Additional information is contained in the original extended abstract.

Redox Active Thiol Sensors of Oxidative and Nitrosative Stress

PubMed Central

2012-01-01

Abstract Significance: The reactivity of the thiol in the side chain of cysteines is exploited by bacterial regulatory proteins that sense and respond to reactive oxygen and nitrogen species. Recent Advances: Charged residues and helix dipoles diminish the pKa of redox active cysteines, resulting in a thiolate that is stabilized by neighboring polar amino acids. The reaction of peroxides with thiolates generates a sulfenic acid (–SOH) intermediate that often gives rise to a reversible disulfide bond. Peroxide-induced intramolecular and intermolecular disulfides and intermolecular mixed disulfides modulate the signaling activity of members of the LysR/OxyR, MarR/OhrR, and RsrA family of transcriptional regulators. Thiol-dependent regulators also help bacteria resist the nitrosative and nitroxidative stress. −SOHs, mixed disulfides, and S-nitrosothiols are some of the post-translational modifications induced by nitrogen oxides in the thiol groups of OxyR and SsrB bacterial regulatory proteins. Sulfenylation, disulfide bond formation, S-thiolation, and S-nitrosylation are reversible modifications amenable to feedback regulation by antioxidant and antinitrosative repair systems. The structural and functional changes engaged in the thiol-dependent sensing of reactive species have been adopted by several regulators to foster bacterial virulence during exposure to products of NADPH phagocyte oxidase and inducible nitric oxide synthase. Critical Issues: Investigations with LysR/OxyR, MarR/OhrR, and RsrA family members have helped in an understanding of the mechanisms by which thiols in regulatory proteins react with reactive species, thereby activating antioxidant and antinitrosative gene expression. Future Directions: To define the determinants that provide selectivity of redox active thiolates for some reactive species but not others is an important challenge for future investigations. Antioxid. Redox Signal. 17, 1201–1214. PMID:22257022

Mono-(2-Ethylhexyl) Phthalate Induces Injury in Human Umbilical Vein Endothelial Cells

PubMed Central

Huang, Qi; Li, Bin-Feng; Chen, Chen; Zhang, Hua-Chuan; Xu, Shun-Qing

2014-01-01

Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a widespread environmental contaminant and has been proved to have potential adverse effects on the reproductive system, carcinogenicity, liver, kidney and developmental toxicities. However, the effect of MEHP on vascular system remains unclear. The main purpose of this study was to evaluate the cytotoxic effects of MEHP on human umbilical endothelial cells (HUVEC) and its possible molecular mechanism. HUVEC cells were treated with MEHP (0, 6.25, 12.5, 25,50 and 100 µM), and the cellular apoptosis and mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In present study, MEHP induced a dose-dependent cell injury in HUVEC cell via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3, -8and -9, and increased ratio of Bax/bcl-2 mRNA and protein expression as well as cytochrome C releasing. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, could effectively block MEHP-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicated that MEHP induced apoptosis in HUVEC cells through a reactive oxygen species-mediated mitochondria-dependent pathway. PMID:24836450

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

PubMed Central

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

2013-01-01

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

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats

PubMed Central

Chiang, Bing-Juin; Chen, Tien-Wen; Chung, Shiu-Dong; Lee, Way-Zen; Chien, Chiang-Ting

2017-01-01

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction. PMID:29285288

View of damaged Apollo 13 Service Module from the Lunar/Command Modules

NASA Image and Video Library

1970-04-17

AS13-58-8464 (17 April 1970) --- This view of the severely damaged Apollo 13 Service Module (SM) was photographed from the Lunar Module/Command Module (LM/CM) following SM jettisoning. Nearest the camera is the Service Propulsion System (SPS) engine and nozzle. An entire SM panel was blown away by the apparent explosion of oxygen tank number two located in Sector 4 of the SM. The apparent rupture of the oxygen tank caused the Apollo 13 crew men to use the Lunar Module (LM) as a "lifeboat".

Enhancement of UVB radiation-mediated apoptosis by knockdown of cytosolic NADP+-dependent isocitrate dehydrogenase in HaCaT cells.

PubMed

Lee, Su Jeong; Park, Jeen-Woo

2014-04-01

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS) that promote apoptotic cell death. We showed that cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) plays an essential role in the control of cellular redox balance and defense against oxidative damage, by supplying NADPH for antioxidant systems. In this study, we demonstrated that knockdown of IDPc expression by RNA interference enhances UVB-induced apoptosis of immortalized human HaCaT keratinocytes. This effect manifested as DNA fragmentation, changes in cellular redox status, mitochondrial dysfunction, and modulation of apoptotic marker expression. Based on our findings, we suggest that attenuation of IDPc expression may protect skin from UVB-mediated damage, by inducing the apoptosis of UV-damaged cells.

The AMP-activated protein kinase beta 1 subunit modulates erythrocyte integrity.

PubMed

Cambridge, Emma L; McIntyre, Zoe; Clare, Simon; Arends, Mark J; Goulding, David; Isherwood, Christopher; Caetano, Susana S; Reviriego, Carmen Ballesteros; Swiatkowska, Agnieszka; Kane, Leanne; Harcourt, Katherine; Adams, David J; White, Jacqueline K; Speak, Anneliese O

2017-01-01

Failure to maintain a normal in vivo erythrocyte half-life results in the development of hemolytic anemia. Half-life is affected by numerous factors, including energy balance, electrolyte gradients, reactive oxygen species, and membrane plasticity. The heterotrimeric AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that acts as a critical regulator of cellular energy balance. Previous roles for the alpha 1 and gamma 1 subunits in the control of erythrocyte survival have been reported. In the work described here, we studied the role of the beta 1 subunit in erythrocytes and observed microcytic anemia with compensatory extramedullary hematopoiesis together with splenomegaly and increased osmotic resistance. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

A triterpenoid from wild bitter gourd inhibits breast cancer cells

NASA Astrophysics Data System (ADS)

Bai, Li-Yuan; Chiu, Chang-Fang; Chu, Po-Chen; Lin, Wei-Yu; Chiu, Shih-Jiuan; Weng, Jing-Ru

2016-03-01

The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated. TCD suppressed the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values at 72 h of 19 and 23 μM, respectively, via a PPARγ-independent manner. TCD induced cell apoptosis accompanied with pleiotrophic biological modulations including down-regulation of Akt-NF-κB signaling, up-regulation of p38 mitogen-activated protein kinase and p53, increased reactive oxygen species generation, inhibition of histone deacetylases protein expression, and cytoprotective autophagy. Together, these findings provided the translational value of TCD and wild bitter gourd as an antitumor agent for patients with breast cancer.

[Mechanisms of signaling associated with reactive nitrogen and oxygen in apoptosis].

PubMed

Piłat, Justyna; Ługowski, Mateusz; Saczko, Jolanta; Choromańska, Anna; Chwiłkowska, Agnieszka; Banaś, Teresa; Kulbacka, Julita

2016-05-01

The knowledge of apoptotic mechanisms is essential in many biologic aspects related to both normal and neoplastic cells. Cell death by apoptosis is a very desirable way to eliminate unwanted cells: prevents release of the cellular content, which, in contrast to necrosis, provides no activation of inflammatory reactions. Apoptosis is a multistep process in where an extremely important role is played by caspases. Functions of caspases and their modifications are fundamental to understanding the signaling pathways responsible for regulation of apoptosis. These enzymes belong to a family of cysteine proteases that have the potential to destroy the enzymatic and structural proteins, and in the final stages of apoptosis, to lead to the disintegration of the cell. Apoptosis can be modulated by certain signaling pathway. © 2016 MEDPRESS.

Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases.

PubMed

Brandes, Ralf P; Weissmann, Norbert; Schröder, Katrin

2014-08-01

The only known function of the Nox family of NADPH oxidases is the production of reactive oxygen species (ROS). Some Nox enzymes show high tissue-specific expression and the ROS locally produced are required for synthesis of hormones or tissue components. In the cardiovascular system, Nox enzymes are low abundant and function as redox-modulators. By reacting with thiols, nitric oxide (NO) or trace metals, Nox-derived ROS elicit a plethora of cellular responses required for physiological growth factor signaling and the induction and adaptation to pathological processes. The interactions of Nox-derived ROS with signaling elements in the cardiovascular system are highly diverse and will be detailed in this article, which is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System". Copyright © 2014 Elsevier Ltd. All rights reserved.

Synthesis of {111} Facet-Exposed MgO with Surface Oxygen Vacancies for Reactive Oxygen Species Generation in the Dark.

PubMed

Hao, Ying-Juan; Liu, Bing; Tian, Li-Gang; Li, Fa-Tang; Ren, Jie; Liu, Shao-Jia; Liu, Ying; Zhao, Jun; Wang, Xiao-Jing

2017-04-12

Seeking a simple and moderate route to generate reactive oxygen species (ROS) for antibiosis is of great interest and challenge. This work demonstrates that molecule transition and electron rearrangement processes can directly occur only through chemisorption interaction between the adsorbed O 2 and high-energy {111} facet-exposed MgO with abundant surface oxygen vacancies (SOVs), hence producing singlet oxygen and superoxide anion radicals without light irradiation. These ROS were confirmed by electron paramagnetic resonance, in situ Raman, and scavenger experiments. Furthermore, heat plays a crucial role for the electron transfer process to accelerate the formation of ·O 2 - , which is verified by temperature kinetic experiments of nitro blue tetrazolium reduction in the dark. Therefore, the presence of oxygen vacancy can be considered as an intensification of the activation process. The designed MgO is acquired in one step via constructing a reduction atmosphere during the combustion reaction process, which has an ability similar to that of noble metal Pd to activate molecular oxygen and can be used as an effective bacteriocide in the dark.

CO2 reactivity and brain oxygen pressure monitoring in severe head injury.

PubMed

Carmona Suazo, J A; Maas, A I; van den Brink, W A; van Santbrink, H; Steyerberg, E W; Avezaat, C J

2000-09-01

To investigate the effect of hyperventilation on cerebral oxygenation after severe head injury. A prospective, observational study. Neurointensive care unit at a university hospital. A total of 90 patients with severe head injury (Glasgow Coma Scale score < or =8), in whom continuous monitoring of brain tissue oxygen pressure (PbrO2) was performed as a measure of cerebral oxygenation. Arterial PCO2 was decreased each day over a 5-day period for 15 mins by increasing minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2 reactivity was calculated. Outcome at 6 months was evaluated according to the Glasgow Outcome Scale. Effective hyperventilation, defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%) of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60 kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2 decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day 1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/- 4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2 was not related to outcome. In later phases in patients with unfavorable outcome, relative reactivity was increased more markedly, reaching statistical significance on day 5. Increased hyperventilation causes a significant reduction in PbrO2, providing further evidence for possible increased risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2 reactivity on day 1 indicates the decreased responsiveness of cerebral microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing. The increasing PbrO2/PaCO2 reactivity from days 2 to 5 suggests that the risk of compromising cerebral oxygenation by hyperventilation may increase over time.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keidar, Michael, E-mail: keidar@gwu.edu; Robert, Eric

Intense research effort over last few decades in low-temperature (or cold) atmospheric plasma application in bioengineering led to the foundation of a new scientific field, plasma medicine. Cold atmospheric plasmas (CAP) produce various chemically reactive species including reactive oxygen species (ROS) and reactive nitrogen species (RNS). It has been found that these reactive species play an important role in the interaction of CAP with prokaryotic and eukaryotic cells triggering various signaling pathways in cells.

Reactive oxygen species generated by a heat shock protein (Hsp) inducing product contributes to Hsp70 production and Hsp70-mediated protective immunity in Artemia franciscana against pathogenic vibrios.

PubMed

Baruah, Kartik; Norouzitallab, Parisa; Linayati, Linayati; Sorgeloos, Patrick; Bossier, Peter

2014-10-01

The cytoprotective role of heat shock protein (Hsp70) described in a variety of animal disease models, including vibriosis in farmed aquatic animals, suggests that new protective strategies relying upon the use of compounds that selectively turn on Hsp genes could be developed. The product Tex-OE® (hereafter referred to as Hspi), an extract from the skin of the prickly pear fruit, Opuntia ficus indica, was previously shown to trigger Hsp70 synthesis in a non-stressful situation in a variety of animals, including in a gnotobiotically (germ-free) cultured brine shrimp Artemia franciscana model system. This model system offers great potential for carrying out high-throughput, live-animal screens of compounds that have health benefit effects. By using this model system, we aimed to disclose the underlying cause behind the induction of Hsp70 by Hspi in the shrimp host, and to determine whether the product affects the shrimp in inducing resistance towards pathogenic vibrios. We provide unequivocal evidences indicating that during the pretreatment period with Hspi, there is an initial release of reactive oxygen species (hydrogen peroxide and/or superoxide anion), generated by the added product, in the rearing water and associated with the host. The reactive molecules generated are the triggering factors responsible for causing Hsp70 induction within Artemia. We have also shown that Hspi acts prophylactically at an optimum dose regimen to confer protection against pathogenic vibrios. This salutary effect was associated with upregulation of two important immune genes, prophenoloxidase and transglutaminase of the innate immune system. These findings suggest that inducers of stress protein (e.g. Hsp70) are potentially important modulator of immune responses and might be exploited to confer protection to cultured shrimp against Vibrio infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cluster reactivity experiments: Employing mass spectrometry to investigate the molecular level details of catalytic oxidation reactions

PubMed Central

Johnson, Grant E.; Tyo, Eric C.; Castleman, A. W.

2008-01-01

Mass spectrometry is the most widely used tool in the study of the properties and reactivity of clusters in the gas phase. In this article, we demonstrate its use in investigating the molecular-level details of oxidation reactions occurring on the surfaces of heterogeneous catalysts via cluster reactivity experiments. Guided ion beam mass spectrometry (GIB-MS) employing a quadrupole–octopole–quadrupole (Q–O–Q) configuration enables mass-selected cluster ions to be reacted with various chemicals, providing insight into the effect of size, stoichiometry, and ionic charge state on the reactivity of catalyst materials. For positively charged tungsten oxide clusters, it is shown that species having the same stoichiometry as the bulk, WO3+, W2O6+, and W3O9+, exhibit enhanced activity and selectivity for the transfer of a single oxygen atom to propylene (C3H6), suggesting the formation of propylene oxide (C3H6O), an important monomer used, for example, in the industrial production of plastics. Furthermore, the same stoichiometric clusters are demonstrated to be active for the oxidation of CO to CO2, a reaction of significance to environmental pollution abatement. The findings reported herein suggest that the enhanced oxidation reactivity of these stoichiometric clusters may be due to the presence of radical oxygen centers (W–O●) with elongated metal–oxygen bonds. The unique insights gained into bulk-phase oxidation catalysis through the application of mass spectrometry to cluster reactivity experiments are discussed. PMID:18687883

Li-air batteries: Importance of singlet oxygen

NASA Astrophysics Data System (ADS)

Luntz, Alan C.; McCloskey, Bryan D.

2017-04-01

The deployment of Li-air batteries is hindered by severe parasitic reactions during battery cycling. Now, the reactive singlet oxygen intermediate is shown to substantially contribute to electrode and electrolyte degradation.

Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

PubMed

Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

2016-05-01

Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions.

Bovine adenovirus 3 core protein precursor pVII localizes to mitochondria, and modulates ATP synthesis, mitochondrial Ca2+ and mitochondrial membrane potential.

PubMed

Anand, Sanjeev K; Gaba, Amit; Singh, Jaswant; Tikoo, Suresh K

2014-02-01

Viruses modulate the functions of mitochondria by translocating viral proteins to the mitochondria. Subcellular fractionation and sensitivity to proteinase K/Triton X-100 treatment of mitochondrial fractions of bovine adenovirus (BAdV)-3-infected/transfected cells suggested that core protein pVII localizes to the mitochondria and contains a functional mitochondrial localization signal. Moreover, mitochondrial localization of BAdV-3 pVII appears to help in the retention of mitochondrial Ca(2+), inducing a significant increase in the levels of ATP and maintaining the mitochondrial membrane potential (MMP) in transfected cells. In contrast, mitochondrial localization of BAdV-3 pVII has no significant effect on the levels of cytoplasmic Ca(2+) and reactive oxygen species production in the transfected cells. Consistent with these results, expression of pVII in transfected cells treated with staurosporine decreased significantly the activation of caspase-3. Our results suggested that BAdV-3 pVII localizes to mitochondria, and interferes with apoptosis by inhibiting loss of the MMP and by increasing mitochondrial Ca(2+) and ATP production.

Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes.

PubMed

Lee, Kyung-Ah; Kim, Boram; Bhin, Jinhyuk; Kim, Do Hun; You, Hyejin; Kim, Eun-Kyoung; Kim, Sung-Hee; Ryu, Ji-Hwan; Hwang, Daehee; Lee, Won-Jae

2015-02-11

Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection. Copyright © 2015 Elsevier Inc. All rights reserved.

The READY program: Building a global potential energy surface and reactive dynamic simulations for the hydrogen combustion.

PubMed

Mogo, César; Brandão, João

2014-06-30

READY (REActive DYnamics) is a program for studying reactive dynamic systems using a global potential energy surface (PES) built from previously existing PESs corresponding to each of the most important elementary reactions present in the system. We present an application to the combustion dynamics of a mixture of hydrogen and oxygen using accurate PESs for all the systems involving up to four oxygen and hydrogen atoms. Results at the temperature of 4000 K and pressure of 2 atm are presented and compared with model based on rate constants. Drawbacks and advantages of this approach are discussed and future directions of research are pointed out. Copyright © 2014 Wiley Periodicals, Inc.

Use of hydrostatic pressure for modulation of protein chemical modification and enzymatic selectivity.

PubMed

Makarov, Alexey A; Helmy, Roy; Joyce, Leo; Reibarkh, Mikhail; Maust, Mathew; Ren, Sumei; Mergelsberg, Ingrid; Welch, Christopher J

2016-05-11

Using hydrostatic pressure to induce protein conformational changes can be a powerful tool for altering the availability of protein reactive sites and for changing the selectivity of enzymatic reactions. Using a pressure apparatus, it has been demonstrated that hydrostatic pressure can be used to modulate the reactivity of lysine residues of the protein ubiquitin with a water-soluble amine-specific homobifunctional coupling agent. Fewer reactive lysine residues were observed when the reaction was carried out under elevated pressure of 3 kbar, consistent with a pressure-induced conformational change of ubiquitin that results in fewer exposed lysine residues. Additionally, modulation of the stereoselectivity of an enzymatic transamination reaction was observed at elevated hydrostatic pressure. In one case, the minor diasteromeric product formed at atmospheric pressure became the major product at elevated pressure. Such pressure-induced alterations of protein reactivity may provide an important new tool for enzymatic reactions and the chemical modification of proteins.

Aquatic Nutrient Simulation Modules (NSMs) Developed for Hydrologic and Hydraulic Models

DTIC Science & Technology

2016-02-01

effect of temperature on algal growth unitless FOxpi oxygen attenuation for algal respiration unitless FOxb oxygen attenuation for benthic algal... effect of temperature below T0p on benthic algal growth 0C-2 ktb2 effect of temperature above T0p on benthic algal growth 0C-2 ka(T) oxygen ...Si Silica SOD Sediment Oxygen Demand SO4 TEMP Sulfate Water Temperature Simulation Module TN Total Nitrogen TP Total Phosphorous TIC Total

Environmental health hazards of e-cigarettes and their components: Oxidants and copper in e-cigarette aerosols.

PubMed

Lerner, Chad A; Sundar, Isaac K; Watson, Richard M; Elder, Alison; Jones, Ryan; Done, Douglas; Kurtzman, Rachel; Ossip, Deborah J; Robinson, Risa; McIntosh, Scott; Rahman, Irfan

2015-03-01

To narrow the gap in our understanding of potential oxidative properties associated with Electronic Nicotine Delivery Systems (ENDS) i.e. e-cigarettes, we employed semi-quantitative methods to detect oxidant reactivity in disposable components of ENDS/e-cigarettes (batteries and cartomizers) using a fluorescein indicator. These components exhibit oxidants/reactive oxygen species reactivity similar to used conventional cigarette filters. Oxidants/reactive oxygen species reactivity in e-cigarette aerosols was also similar to oxidant reactivity in cigarette smoke. A cascade particle impactor allowed sieving of a range of particle size distributions between 0.450 and 2.02 μm in aerosols from an e-cigarette. Copper, being among these particles, is 6.1 times higher per puff than reported previously for conventional cigarette smoke. The detection of a potentially cytotoxic metal as well as oxidants from e-cigarette and its components raises concern regarding the safety of e-cigarettes use and the disposal of e-cigarette waste products into the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles

NASA Astrophysics Data System (ADS)

Lavado, Andrea S.; Chauhan, Veeren M.; Alhaj Zen, Amer; Giuntini, Francesca; Jones, D. Rhodri E.; Boyle, Ross W.; Beeby, Andrew; Chan, Weng C.; Aylott, Jonathan W.

2015-08-01

Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(ii) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(ii) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(ii) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures. Electronic supplementary information (ESI) available: Materials and experimental methods for the synthesis of (1) positively charged alkyne functionalized nanoparticles (2) Zn(ii) and Cu(ii) centred porphyrin (3); conjugating porphyrins to alkyne-functionalized nanoparticles via click chemistry (4) nanoparticle characterisation (size charge and fluorescence), (5) synthesis of BPTFMC (6) hMSC collection, storage and preparation (7) delivery of porphyrin functionalized nanoparticles (8) staining mitochondria, cumulative ROS production and determination of nanoparticles subcellular localisation (9) fluorescence microscopy and controlled irradiation of hMSCs (10) flow cytometry and controlled irradiation using a custom built irradiator. In addition, results highlighting: (1) nanoparticles emission spectra, size and charge, (2) BPTFMC fluorescence response and (3) hMSCs following light irradiation using flow cytometry. See DOI: 10.1039/c5nr00795j

Reactive Oxygen Species and Mitochondrial Homeostasis as Regulators of Stem Cell Fate and Function.

PubMed

Tan, Darren Q; Suda, Toshio

2018-07-10

The precise role and impact of reactive oxygen species (ROS) in stem cells, which are essential for lifelong tissue homeostasis and regeneration, remain of significant interest to the field. The long-term regenerative potential of a stem cell compartment is determined by the delicate balance between quiescence, self-renewal, and differentiation, all of which can be influenced by ROS levels. Recent Advances: The past decade has seen a growing appreciation for the importance of ROS and redox homeostasis in various stem cell compartments, particularly those of hematopoietic, neural, and muscle tissues. In recent years, the importance of proteostasis and mitochondria in relation to stem cell biology and redox homeostasis has garnered considerable interest. Here, we explore the reciprocal relationship between ROS and stem cells, with significant emphasis on mitochondria as a core component of redox homeostasis. We discuss how redox signaling, involving cell-fate determining protein kinases and transcription factors, can control stem cell function and fate. We also address the impact of oxidative stress on stem cells, especially oxidative damage of lipids, proteins, and nucleic acids. We further discuss ROS management in stem cells, and present recent evidence supporting the importance of mitochondrial activity and its modulation (via mitochondrial clearance, biogenesis, dynamics, and distribution [i.e., segregation and transfer]) in stem cell redox homeostasis. Therefore, elucidating the intricate links between mitochondria, cellular metabolism, and redox homeostasis is envisioned to be critical for our understanding of ROS in stem cell biology and its therapeutic relevance in regenerative medicine. Antioxid. Redox Signal. 00, 000-000.

Crucial yet divergent roles of mitochondrial redox state in skeletal muscle vs. brown adipose tissue energetics.

PubMed

Mailloux, Ryan J; Adjeitey, Cyril Nii-Klu; Xuan, Jian Ying; Harper, Mary-Ellen

2012-01-01

Reduced glutathione (GSH) is the major determinant of redox balance in mitochondria and as such is fundamental in the control of cellular bioenergetics. GSH is also the most important nonprotein antioxidant molecule in cells. Surprisingly, the effect of redox environment has never been examined in skeletal muscle and brown adipose tissue (BAT), two tissues that have exceptional dynamic range and that are relevant to the development of obesity and related diseases. Here, we show that the redox environment plays crucial, yet divergent, roles in modulating mitochondrial bioenergetics in skeletal muscle and BAT. Skeletal muscle mitochondria were found to naturally have a highly reduced environment (GSH/GSSG≈46), and this was associated with fairly high (∼40%) rates of state 4 (nonphosphorylating) respiration and decreased reactive oxygen species (ROS) emission. The deglutathionylation of uncoupling protein 3 (UCP3) following an increase in the reductive potential of mitochondria results in a further increase in nonphosphorylating respiration (∼20% in situ). BAT mitochondria were found to have a much more oxidized status (GSH/GSSG≈13) and had basal reactive oxygen species emission that was higher (∼250% increase in ROS generation) than that in skeletal muscle mitochondria. When redox status was subsequently increased (i.e., more reduced), UCP1-mediated uncoupling was more sensitive to GDP inhibition. Surprisingly, BAT was found to be devoid of glutaredoxin-2 (Grx2) expression, while there was abundant expression in skeletal muscle. Taken together, these findings reveal the importance of redox environment in controlling bioenergetic functions in both tissues, and the highly unique characteristics of BAT in this regard.

Physalis angulata induces death of promastigotes and amastigotes of Leishmania (Leishmania) amazonensis via the generation of reactive oxygen species.

PubMed

Da Silva, B J M; Da Silva, R R P; Rodrigues, A P D; Farias, L H S; Do Nascimento, J L M; Silva, E O

2016-03-01

Leishmaniasis are a neglected group of emerging diseases that have been found in 98 countries and are caused by protozoa of the genus Leishmania. The therapy for leishmaniasis causes several side effects and leads to drug-resistant strains. Natural products from plants have exhibited activities against Leishmania in various experimental models. Physalis angulata is a widely used plant in popular medicine, and in the literature it has well-documented leishmanicidal activity. However, its mechanism of action is still unknown. Thus, this study aims to evaluate the mechanism driving the leishmanicidal activity of an aqueous extract of P. angulata root (AEPa). AEPa was effective against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. This effect was mediated by an increase of reactive oxygen species (ROS), but not of nitric oxide (NO). The increased production of ROS induces cell death by phenotypes seems by apoptosis cell death in Leishmania, but not autophagy or necrosis. In addition, morphological analysis of macrophages showed that AEPa induced a high number of cytoplasmic projections, increased the volume of cytoplasm and number of vacuoles, caused cytoskeleton alterations and resulted in high spreading ability. AEPa also promoted superoxide anion (O2(-)) production in both uninfected macrophages and those infected with Leishmania. Therefore, these results revealed that AEPa causes cell death by phenotypes seems by apoptosis cell death in L. amazonensis and modulates macrophage activation through morphofunctional alterations and O2(-) generation to induce Leishmania death. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional Redundancy and Divergence within the Arabidopsis RETICULATA-RELATED Gene Family1[W][OA

PubMed Central

Pérez-Pérez, José Manuel; Esteve-Bruna, David; González-Bayón, Rebeca; Kangasjärvi, Saijaliisa; Caldana, Camila; Hannah, Matthew A.; Willmitzer, Lothar; Ponce, María Rosa; Micol, José Luis

2013-01-01

A number of Arabidopsis (Arabidopsis thaliana) mutants exhibit leaf reticulation, having green veins that stand out against paler interveinal tissues, fewer cells in the interveinal mesophyll, and normal perivascular bundle sheath cells. Here, to examine the basis of leaf reticulation, we analyzed the Arabidopsis RETICULATA-RELATED (RER) gene family, several members of which cause leaf reticulation when mutated. Although transcripts of RE, RER1, and RER3 were mainly detected in the bundle sheath cells of expanded leaves, functional RER3:GREEN FLUORESCENT PROTEIN was visualized in the chloroplast membranes of all photosynthetic cells. Leaf reticulation in the re and rer3 loss-of-function mutants occurred, along with accumulation of reactive oxygen species, in a photoperiod-dependent manner. A comparison of re and rer3 leaf messenger RNA expression profiles showed more than 200 genes were similarly misexpressed in both mutants. In addition, metabolic profiles of mature leaves revealed that several biosynthetic pathways downstream of pyruvate are altered in re and rer3. Double mutant analysis showed that only re rer1 and rer5 rer6 exhibited synergistic phenotypes, indicating functional redundancy. The redundancy between RE and its closest paralog, RER1, was confirmed by overexpressing RER1 in re mutants, which partially suppressed leaf reticulation. Our results show that RER family members can be divided into four functional modules with divergent functions. Moreover, these results provide insights into the origin of the reticulated phenotype, suggesting that the RER proteins functionally interconnect photoperiodic growth, amino acid homeostasis, and reactive oxygen species metabolism during Arabidopsis leaf growth. PMID:23596191

Programmed death-1 controls T cell survival by regulating oxidative metabolism1

PubMed Central

Tkachev, Victor; Goodell, Stefanie; Opipari, Anthony W.; Hao, Ling-Yang; Franchi, Luigi; Glick, Gary D.; Ferrara, James L.M.; Byersdorfer, Craig A.

2015-01-01

The co-inhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly up-regulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1HiROSHi phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and total cellular ROS levels and PD-1 driven increases in ROS were dependent upon the oxidation of fatty acids, as treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by anti-oxidants. Furthermore, PD-1 driven changes in ROS were fundamental to establishing a cell’s susceptibility to subsequent metabolic inhibition, as blockade of PD-1 decreased the efficacy of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing reactive oxygen species in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti-PD-1 therapies in the clinic. PMID:25972478

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

PubMed Central

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants. PMID:29033963

In vitro bioassessment of the immunomodulatory activity of Saccharomyces cerevisiae components using bovine macrophages and Mycobacterium avium ssp. paratuberculosis.

PubMed

Li, Z; Kang, H; You, Q; Ossa, F; Mead, P; Quinton, M; Karrow, N A

2018-04-11

The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S. cerevisiae components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic activity, reactive oxygen species production, and immune-related gene (IL6, IL10, IL12p40, IL13, IL23), transforming growth factor β, ARG1, CASP1, and inducible nitric oxide synthase expression were investigated when BOMAC were cocultured with cell wall components from 4 different strains (A, B, C, and D) and 2 forms of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was concentration-dependently attenuated when BOMAC were cocultured with yeast components for 6 h. Each yeast derivative also induced a concentration-dependent increase in BOMAC reactive oxygen species production after a 6-h exposure. In addition, BOMAC mRNA expression of the immune-related genes was investigated after 6 and 24 h of exposure to yeast components. All yeast components were found to regulate the immunomodulatory genes of BOMAC; however, the response varied among components and over time. The in vitro bioassessment studies reported here suggest that dead yeast and its cell wall components may be useful for modulating macrophage function before or during MAP infection. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reactive Oxygen Species/Nitric Oxide Mediated Inter-Organ Communication in Skeletal Muscle Wasting Diseases

PubMed Central

Leitner, Lucia M.; Wilson, Rebecca J.; Yan, Zhen

2017-01-01

Abstract Significance: Cachexia is defined as a complex metabolic syndrome that is associated with underlying illness and a loss of muscle with or without loss of fat mass. This disease is associated with a high incidence with chronic diseases such as heart failure, cancer, chronic obstructive pulmonary disease (COPD), and acquired immunodeficiency syndrome (AIDS), among others. Since there is currently no effective treatment available, cachectic patients have a poor prognosis. Elucidation of the underlying mechanisms is, therefore, an important medical task. Recent Advances: There is accumulating evidence that the diseased organs such as heart, lung, kidney, or cancer tissue secrete soluble factors, including Angiotensin II, myostatin (growth differentiation factor 8 [GDF8]), GDF11, tumor growth factor beta (TGFβ), which act on skeletal muscle. There, they induce a set of genes called atrogenes, which, among others, induce the ubiquitin-proteasome system, leading to protein degradation. Moreover, elevated reactive oxygen species (ROS) levels due to modulation of NADPH oxidases (Nox) and mitochondrial function contribute to disease progression, which is characterized by loss of muscle mass, exercise resistance, and frailty. Critical issues: Although substantial progress was achieved to elucidate the pathophysiology of cachexia, effectice therapeutic strategies are urgently needed. Future Directions: With the identification of key components of the aberrant inter-organ communication leading to cachexia, studies in mice and men to inhibit ROS formation, induction of anti-oxidative superoxide dismutases, and upregulation of muscular nitric oxide (NO) formation either by pharmacological tools or by exercise are promising approaches to reduce the extent of skeletal muscle wasting. Antioxid. Redox Signal. 26, 700–717. PMID:27835923

Pycnogenol® inhibits lipid accumulation in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production associated with antioxidant enzyme responses.

PubMed

Lee, Ok-Hwan; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Boo-Yong

2012-03-01

Pycnogenol® is a group of flavonoids with antioxidant effects. Adipogenesis is the process of adipocyte differentiation. It causes the increase of lipids as well as ROS (reactive oxygen species). Lipid accumulation and ROS production were determined in 3 T3-L1 adipocyte, and the effect of Pycnogenol® was evaluated. Lipid accumulation was elevated in adipocyte treated with hydrogen peroxide, one of the ROS. Pycnogenol® showed an inhibitory effect on the lipid accumulation and ROS production during the adipogenesis. We also investigated the molecular events associated with ROS production and lipid accumulation. Our results showed that Pycnogenol® inhibited the mRNA expression of pro-oxidant enzymes, such as NOX4 (NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 4), and the NADPH-producing G6PDH (glucose-6-phosphate dehydrogenase) enzyme. In addition, Pycnogenol® suppressed the mRNA abundance of adipogenic transcription factors, PPAR-γ (peroxisome proliferator-activated receptor γ) and C/EBP-α (CCAAT/enhancer binding protein α), and their target gene, aP2 (adipocyte protein 2) responsible for fatty acid transportation. On the other hand, Pycnogenol® increased the abundance of antioxidant proteins such as Cu/Zn-SOD (copper-zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and GR (glutathione reductase). Our results suggest that Pycnogenol® inhibits lipid accumulation and ROS production by regulating adipogenic gene expression and pro-/antioxidant enzyme responses in adipocytes. Copyright © 2011 John Wiley & Sons, Ltd.

Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens.

PubMed

Liu, Y X; Guo, Y M; Wang, Z

2007-02-01

1. The objective of the present study was to investigate the effect of magnesium (Mg) on reactive oxygen species (ROS) production in the thigh muscles of broiler chickens. A total of 96 1-d-old male Arbor Acre broiler chickens were randomly allocated into two groups, fed either on low-Mg or control diets containing about 1.2 g/kg or 2.4 g Mg/kg dry matter. 2. The low-Mg diet significantly increased malondialdehyde (MDA) concentration and decreased glutathione (GSH) in the thigh muscles of broiler chickens. ROS production in the thigh muscle homogenate was significantly higher in the low-Mg group than in the control group. Compared with the control, muscle Mg concentration of broiler chickens from the low-Mg group decreased by 9.5%. 3. Complex II and III activities of the mitochondrial electron transport chain in broilers on low-Mg diet increased by 23 and 35%, respectively. Significant negative correlations between ROS production and the activities of mitochondrial electron transport chain (ETC) complexes were observed. 4. The low-Mg diet did not influence contents of iron (Fe) or calcium (Ca) in the thigh muscles of broiler chickens and did not influence unsaturated fatty acid composition (except C18:2) in the thigh muscles. 5. A low-Mg diet decreased Mg concentration in the thigh muscles of broiler chickens and then induced higher activities of mitochondrial ETC, consequently increasing ROS production. These results suggest that Mg modulates the oxidation-anti-oxidation system of the thigh muscles at least partly through affecting ROS production.

Increased reactive oxygen species production during reductive stress: The roles of mitochondrial glutathione and thioredoxin reductases.

PubMed

Korge, Paavo; Calmettes, Guillaume; Weiss, James N

2015-01-01

Both extremes of redox balance are known to cause cardiac injury, with mounting evidence revealing that the injury induced by both oxidative and reductive stress is oxidative in nature. During reductive stress, when electron acceptors are expected to be mostly reduced, some redox proteins can donate electrons to O2 instead, which increases reactive oxygen species (ROS) production. However, the high level of reducing equivalents also concomitantly enhances ROS scavenging systems involving redox couples such as NADPH/NADP+ and GSH/GSSG. Here our objective was to explore how reductive stress paradoxically increases net mitochondrial ROS production despite the concomitant enhancement of ROS scavenging systems. Using recombinant enzymes and isolated permeabilized cardiac mitochondria, we show that two normally antioxidant matrix NADPH reductases, glutathione reductase and thioredoxin reductase, generate H2O2 by leaking electrons from their reduced flavoprotein to O2 when electron flow is impaired by inhibitors or because of limited availability of their natural electron acceptors, GSSG and oxidized thioredoxin. The spillover of H2O2 under these conditions depends on H2O2 reduction by peroxiredoxin activity, which may regulate redox signaling in response to endogenous or exogenous factors. These findings may explain how ROS production during reductive stress overwhelms ROS scavenging capability, generating the net mitochondrial ROS spillover causing oxidative injury. These enzymes could potentially be targeted to increase cancer cell death or modulate H2O2-induced redox signaling to protect the heart against ischemia/reperfusion damage. Copyright © 2015 Elsevier B.V. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yun, Hong Shik; Hong, Eun-Hee; Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul 133-791

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 phenotypemore » 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.« less

ATP-binding cassette transporter 1 participates in LDL oxidation by artery wall cells.

PubMed

Reddy, Srinivasa T; Hama, Susan; Ng, Carey; Grijalva, Victor; Navab, Mohamad; Fogelman, Alan M

2002-11-01

We have previously reported that products of the lipoxygenase pathway, hydroperoxyoctadecadienoic acid and hydroperoxyeicosatetraenoic acid, as well as cholesterol linoleate hydroperoxides, collectively termed seeding molecules, are removed by apolipoprotein A-I (apoA-I) from the artery wall cells and render low density lipoprotein (LDL) resistant to oxidation by human artery wall cells. The mechanisms by which oxidized lipids are transported and/or transferred to lipoproteins and the pathways by which apoA-I facilitates their removal remain unclear. ATP-binding cassette transporter 1 (ABCA1) is known to facilitate the release of cellular phospholipids and cholesterol from the plasma membrane to apoA-I and high density lipoprotein. Therefore, we evaluated whether ABCA1 participates in LDL oxidation. In this report, we show that (1) chemical inhibitors of ABCA1 function, glyburide and DIDS, block artery wall cell-mediated oxidative modification of LDL, (2) inhibition of ABCA1 with the use of antisense (but not sense) oligonucleotides prevents LDL-induced lipid hydroperoxide formation and LDL-induced monocyte chemotactic activity by the artery wall cells, and (3) oxysterols that induce ABCA1 expression, such as 22(R)hydroxycholesterol, enhance cell-mediated LDL oxidation. Furthermore, we also show that 22(R)hydroxycholesterol induces the production of reactive oxygen species in the artery wall cells, which can be removed by incubating the artery wall cells with apoA-I. Our data suggest that ABCA1 plays an important role in artery wall cell-mediated modification/oxidation of LDL by modulating the release of reactive oxygen species from artery wall cells that are necessary for LDL oxidation.

Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.

PubMed

Ambrus, Attila; Mizsei, Reka; Adam-Vizi, Vera

2015-07-01

Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of the human alpha-ketoglutarate dehydrogenase complex (α-KGDHc) and few other dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death; the pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). It has been shown by our laboratory that selected pathogenic mutations, besides lowering the physiological activity of hLADH, significantly stimulate ROS generation by hLADH, especially at lower pH, which might play a role in the pathogenesis of E3-deficiency in respective cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH hLADH structure and analyzed the structural changes induced in this structure by eight of the pathogenic mutations of hLADH. In the absence of high resolution mutant structures these pieces of information are crucial for the mechanistic investigation of the molecular pathogeneses of the hLADH protein. In the present work we analyzed by molecular dynamics simulation the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the structures of these disease-causing mutants of hLADH have never been examined before.

Cytological and Proteomic Analyses of Osmunda cinnamomea Germinating Spores Reveal Characteristics of Fern Spore Germination and Rhizoid Tip Growth.

PubMed

Suo, Jinwei; Zhao, Qi; Zhang, Zhengxiu; Chen, Sixue; Cao, Jian'guo; Liu, Guanjun; Wei, Xing; Wang, Tai; Yang, Chuanping; Dai, Shaojun

2015-09-01

Fern spore is a good single-cell model for studying the sophisticated molecular networks in asymmetric cell division, differentiation, and polar growth. Osmunda cinnamomea L. var. asiatica is one of the oldest fern species with typical separate-growing trophophyll and sporophyll. The chlorophyllous spores generated from sporophyll can germinate without dormancy. In this study, the spore ultrastructure, antioxidant enzyme activities, as well as protein and gene expression patterns were analyzed in the course of spore germination at five typical stages (i.e. mature spores, rehydrated spores, double-celled spores, germinated spores, and spores with protonemal cells). Proteomic analysis revealed 113 differentially expressed proteins, which were mainly involved in photosynthesis, reserve mobilization, energy supplying, protein synthesis and turnover, reactive oxygen species scavenging, signaling, and cell structure modulation. The presence of multiple proteoforms of 25 differentially expressed proteins implies that post-translational modification may play important roles in spore germination. The dynamic patterns of proteins and their encoding genes exhibited specific characteristics in the processes of cell division and rhizoid tip growth, which include heterotrophic and autotrophic metabolisms, de novo protein synthesis and active protein turnover, reactive oxygen species and hormone (brassinosteroid and ethylene) signaling, and vesicle trafficking and cytoskeleton dynamic. In addition, the function skew of proteins in fern spores highlights the unique and common mechanisms when compared with evolutionarily divergent spermatophyte pollen. These findings provide an improved understanding of the typical single-celled asymmetric division and polar growth during fern spore germination. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Altered Antioxidant System Stimulates Dielectric Barrier Discharge Plasma-Induced Cell Death for Solid Tumor Cell Treatment

PubMed Central

Park, Daehoon; Choi, Eun H.

2014-01-01

This study reports the experimental findings and plasma delivery approach developed at the Plasma Bioscience Research Center, Korea for the assessment of antitumor activity of dielectric barrier discharge (DBD) for cancer treatment. Detailed investigation of biological effects occurring after atmospheric pressure non-thermal (APNT) plasma application during in vitro experiments revealed the role of reactive oxygen species (ROS) in modulation of the antioxidant defense system, cellular metabolic activity, and apoptosis induction in cancer cells. To understand basic cellular mechanisms, we investigated the effects of APNT DBD plasma on antioxidant defense against oxidative stress in various malignant cells as well as normal cells. T98G glioblastoma, SNU80 thyroid carcinoma, KB oral carcinoma and a non-malignant HEK293 embryonic human cell lines were treated with APNT DBD plasma and cellular effects due to reactive oxygen species were observed. Plasma significantly decreased the metabolic viability and clonogenicity of T98G, SNU80, KB and HEK293 cell lines. Enhanced ROS in the cells led to death via alteration of total antioxidant activity, and NADP+/NADPH and GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by annexin V-FITC and propidium iodide staining. These consequences suggested that the failure of antioxidant defense machinery, with compromised redox status, might have led to sensitization of the malignant cells. These findings suggest a promising approach for solid tumor therapy by delivering a lethal dose of APNT plasma to tumor cells while sparing normal healthy tissues. PMID:25068311

DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer

PubMed Central

Evans, Lynda; Duchnowska, Renata; Reed, L. Tiffany; Palmieri, Diane; Qian, Yongzhen; Badve, Sunil; Sledge, George; Gril, Brunilde; Aladjem, Mirit I.; Fu, Haiqing; Flores, Natasha M.; Gökmen-Polar, Yesim; Biernat, Wojciech; Szutowicz-Zielińska, Ewa; Mandat, Tomasz; Trojanowski, Tomasz; Och, Waldemar; Czartoryska-Arlukowicz, Bogumiła; Jassem, Jacek; Mitchell, James B.

2014-01-01

Background Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood. Methods Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis–specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group). Results Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression. Conclusions BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species–mediated genotoxic stress in the metastatic brain. PMID:24948741

DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer.

PubMed

Woditschka, Stephan; Evans, Lynda; Duchnowska, Renata; Reed, L Tiffany; Palmieri, Diane; Qian, Yongzhen; Badve, Sunil; Sledge, George; Gril, Brunilde; Aladjem, Mirit I; Fu, Haiqing; Flores, Natasha M; Gökmen-Polar, Yesim; Biernat, Wojciech; Szutowicz-Zielińska, Ewa; Mandat, Tomasz; Trojanowski, Tomasz; Och, Waldemar; Czartoryska-Arlukowicz, Bogumiła; Jassem, Jacek; Mitchell, James B; Steeg, Patricia S

2014-07-01

Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood. Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group). Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression. BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species-mediated genotoxic stress in the metastatic brain. Published by Oxford University Press 2014.

Reactive Coevaporation Synthesis and Characterization of SrTiO3 Thin Films

NASA Astrophysics Data System (ADS)

Yamaguchi, Hiromu; Matsubara, Shogo; Miyasaka, Yoichi

1991-09-01

SrTiO3 thin films were prepared by the reactive coevaporation method, where the Ti and Sr metals were evaporated in oxygen ambient with an E-gun and K-cell, respectively. A uniform depth profile in composition was achieved by altering the Ti evaporation rate according to the Sr evaporation rate change. A typical dielectric constant of 170 was measured on films of 75 nm in thickness. The in-situ annealing in oxygen plasma reduced the leakage current.

The Comparative Study of the Effects of Extremely Low Frequency Electromagnetic Fields and Infrasound on Water Molecule Dissociation and Generation of Reactive Oxygen Species

DTIC Science & Technology

2008-11-01

ISTC Project No. #1592P The Comparative Study of The Effects of Extremely Low Frequency Electromagnetic Fields and Infrasound on Water Molecule...performed under the agreement with the International Science and Technology Center ( ISTC ), Moscow. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704...dissociation and generation of reactive oxygen spaces. 5a. CONTRACT NUMBER ISTC Registration No: A-1592p 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Ion transport membrane module and vessel system

DOEpatents

Stein, VanEric Edward; Carolan, Michael Francis; Chen, Christopher M.; Armstrong, Phillip Andrew; Wahle, Harold W.; Ohrn, Theodore R.; Kneidel, Kurt E.; Rackers, Keith Gerard; Blake, James Erik; Nataraj, Shankar; van Doorn, Rene Hendrik Elias; Wilson, Merrill Anderson

2007-02-20

An ion transport membrane system comprising (a) a pressure vessel having an interior, an exterior, an inlet, and an outlet; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein any inlet and any outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; and (c) one or more gas manifolds in flow communication with interior regions of the membrane modules and with the exterior of the pressure vessel. The ion transport membrane system may be utilized in a gas separation device to recover oxygen from an oxygen-containing gas or as an oxidation reactor to oxidize compounds in a feed gas stream by oxygen permeated through the mixed metal oxide ceramic material of the membrane modules.

Ion transport membrane module and vessel system

DOEpatents

Stein, VanEric Edward [Allentown, PA; Carolan, Michael Francis [Allentown, PA; Chen, Christopher M [Allentown, PA; Armstrong, Phillip Andrew [Orefield, PA; Wahle, Harold W [North Canton, OH; Ohrn, Theodore R [Alliance, OH; Kneidel, Kurt E [Alliance, OH; Rackers, Keith Gerard [Louisville, OH; Blake, James Erik [Uniontown, OH; Nataraj, Shankar [Allentown, PA; Van Doorn, Rene Hendrik Elias; Wilson, Merrill Anderson [West Jordan, UT

2012-02-14

An ion transport membrane system comprising (a) a pressure vessel having an interior, an exterior, an inlet, and an outlet; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein any inlet and any outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; and (c) one or more gas manifolds in flow communication with interior regions of the membrane modules and with the exterior of the pressure vessel. The ion transport membrane system may be utilized in a gas separation device to recover oxygen from an oxygen-containing gas or as an oxidation reactor to oxidize compounds in a feed gas stream by oxygen permeated through the mixed metal oxide ceramic material of the membrane modules.

Ion transport membrane module and vessel system

DOEpatents

Stein, VanEric Edward [Allentown, PA; Carolan, Michael Francis [Allentown, PA; Chen, Christopher M [Allentown, PA; Armstrong, Phillip Andrew [Orefield, PA; Wahle, Harold W [North Canton, OH; Ohrn, Theodore R [Alliance, OH; Kneidel, Kurt E [Alliance, OH; Rackers, Keith Gerard [Louisville, OH; Blake, James Erik [Uniontown, OH; Nataraj, Shankar [Allentown, PA; van Doorn, Rene Hendrik Elias; Wilson, Merrill Anderson [West Jordan, UT

2008-02-26

An ion transport membrane system comprising (a) a pressure vessel having an interior, an exterior, an inlet, and an outlet; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein any inlet and any outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; and (c) one or more gas manifolds in flow communication with interior regions of the membrane modules and with the exterior of the pressure vessel.The ion transport membrane system may be utilized in a gas separation device to recover oxygen from an oxygen-containing gas or as an oxidation reactor to oxidize compounds in a feed gas stream by oxygen permeated through the mixed metal oxide ceramic material of the membrane modules.

Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO

PubMed Central

Sun, Junhui; Xin, Chunlin; Eu, Jerry P.; Stamler, Jonathan S.; Meissner, Gerhard

2001-01-01

We have shown previously that at physiologically relevant oxygen tension (pO2 ≈ 10 mmHg), NO S-nitrosylates 1 of ≈50 free cysteines per ryanodine receptor 1 (RyR1) subunit and transduces a calcium-sensitizing effect on the channel by means of calmodulin (CaM). It has been suggested that cysteine-3635 is part of a CaM-binding domain, and its reactivity is attenuated by CaM [Porter Moore, C., Zhang, J. Z., Hamilton, S. L. (1999) J. Biol. Chem. 274, 36831–36834]. Therefore, we tested the hypothesis that the effect of NO was mediated by C3635. The full-length RyR1 single-site C3635A mutant was generated and expressed in HEK293 cells. The mutation resulted in the loss of CaM-dependent NO modulation of channel activity and reduced S-nitrosylation by NO to background levels but did not affect NO-independent channel modulation by CaM or the redox sensitivity of the channel to O2 and glutathione. Our results reveal that different cysteines within the channel have been adapted to serve in nitrosative and oxidative responses, and that S-nitrosylation of the cysteine-containing CaM-binding domain underlies the mechanism of CaM-dependent regulation of RyR1 by NO. PMID:11562475

Allosteric modulation of ATP-gated P2X receptor channels

PubMed Central

Coddou, Claudio; Stojilkovic, Stanko S.; Huidobro-Toro, J. Pablo

2013-01-01

Seven mammalian purinergic receptor subunits, denoted P2X1 to P2X7, and several spliced forms of these subunits have been cloned. When heterologously expressed, these cDNAs encode ATP-gated non-selective cation channels organized as trimers. All activated receptors produce cell depolarization and promote Ca2+ influx through their pores and indirectly by activating voltage-gated calcium channels. However, the biophysical and pharmacological properties of these receptors differ considerably, and the majority of these subunits are also capable of forming heterotrimers with other members of the P2X receptor family, which confers further different properties. These channels have three ATP binding domains, presumably located between neighboring subunits, and occupancy of at least two binding sites is needed for their activation. In addition to the orthosteric binding sites for ATP, these receptors have additional allosteric sites that modulate the agonist action at receptors, including sites for trace metals, protons, neurosteroids, reactive oxygen species and phosphoinositides. The allosteric regulation of P2X receptors is frequently receptor-specific and could be a useful tool to identify P2X members in native tissues and their roles in signaling. The focus of this review is on common and receptor-specific allosteric modulation of P2X receptors and the molecular base accounting for allosteric binding sites. PMID:21639805

Mitochondrial modulators in experimental Huntington's disease: reversal of mitochondrial dysfunctions and cognitive deficits.

PubMed

Mehrotra, Arpit; Kanwal, Abhinav; Banerjee, Sanjay Kumar; Sandhir, Rajat

2015-06-01

Huntington's disease (HD) is a chronic neurodegenerative condition involving impaired mitochondrial functions. The present study evaluates the therapeutic potential of combined administration of mitochondrial modulators: alpha-lipoic acid and acetyl-l-carnitine on mitochondrial dysfunctions in 3-NP-induced HD. Our results reveal 3-NP administration resulted in compromise of mitochondrial functions in terms of: (1) impaired activity of mitochondrial respiratory chain enzymes, altered cytochrome levels, reduced histochemical staining of complex-II and IV, reduced in-gel activity of complex-I to V, and reduced mRNA expression of respiratory chain complexes; (2) enhanced mitochondrial oxidative stress indicated by increased malondialdehyde, protein carbonyls, reactive oxygen species and nitrite levels, along with decreased Mn-superoxide dismutase and catalase activity; (3) mitochondrial structural changes measured by mitochondrial swelling, reduced mitochondrial membrane potential and ultra-structure changes; (4) increased cytosolic cytochrome c levels, caspase-3 and -9 activity along with altered expression of apoptotic proteins (AIF, Bim, Bad, and Bax); and (5) impaired cognitive functions assessed using Morris water maze and Y-maze. Combination of mitochondrial modulators (alpha-lipoic acid + acetyl-l-carnitine) on the other hand ameliorated 3-NP-induced mitochondrial dysfunctions, oxidative stress, histologic alterations, and behavioral deficits, suggesting their therapeutic efficacy in the management of HD. Copyright © 2015 Elsevier Inc. All rights reserved.

Isoliquiritigenin-Induced Differentiation in Mouse Melanoma B16F0 Cell Line

PubMed Central

Chen, Xiaoyu; Zhang, Bo; Yuan, Xuan; Yang, Fan; Liu, Jinglei; Zhao, Hong; Liu, Liangliang; Wang, Yanming; Wang, Zhenhua; Zheng, Qiusheng

2012-01-01

The chemotherapeutical treatment is very limited for malignant melanoma, a highly lethal disease occurs globally. Natural products derived from traditional Chinese medicine licorice are attractive in quest new treatments due to their anti-tumor activities. A new dietary flavonoid isoliquiritigenin (ISL) were thus investigated to indentify its anti-melanoma activities on mouse melanoma B16F0 cells in present study. Using biochemical and free radical biological experiments in vitro, we identified the pro-differentiated profiles of ISL and evaluated the role of reactive oxygen species (ROS) during B16F0 cell differentiation. The data showed a strong dose-response relationship between ISL exposure and the characteristics of B16F0 differentiation in terms of morphology changes and melanogenesis. The accumulated intercellular ROS during exposure are necessary to support ISL-induced differentiation, which was proven by additional redox modulators. It was confirmed further by the relative activities of enzymes and genes modulated melanogenesis in ISL-treatments with or without ROS modulators. The tumorigenicity of ISL-treated cells was limited significantly by using the colony formation assay in vitro and an animal model assay in vivo respectively. Our research demonstrated that isoliquiritigenin is a differentiation-inducing agent, and its mechanisms involve ROS accumulation facilitating melanogenesis. PMID:23304254

Isoliquiritigenin-induced differentiation in mouse melanoma B16F0 cell line.

PubMed

Chen, Xiaoyu; Zhang, Bo; Yuan, Xuan; Yang, Fan; Liu, Jinglei; Zhao, Hong; Liu, Liangliang; Wang, Yanming; Wang, Zhenhua; Zheng, Qiusheng

2012-01-01

The chemotherapeutical treatment is very limited for malignant melanoma, a highly lethal disease occurs globally. Natural products derived from traditional Chinese medicine licorice are attractive in quest new treatments due to their anti-tumor activities. A new dietary flavonoid isoliquiritigenin (ISL) were thus investigated to indentify its anti-melanoma activities on mouse melanoma B16F0 cells in present study. Using biochemical and free radical biological experiments in vitro, we identified the pro-differentiated profiles of ISL and evaluated the role of reactive oxygen species (ROS) during B16F0 cell differentiation. The data showed a strong dose-response relationship between ISL exposure and the characteristics of B16F0 differentiation in terms of morphology changes and melanogenesis. The accumulated intercellular ROS during exposure are necessary to support ISL-induced differentiation, which was proven by additional redox modulators. It was confirmed further by the relative activities of enzymes and genes modulated melanogenesis in ISL-treatments with or without ROS modulators. The tumorigenicity of ISL-treated cells was limited significantly by using the colony formation assay in vitro and an animal model assay in vivo respectively. Our research demonstrated that isoliquiritigenin is a differentiation-inducing agent, and its mechanisms involve ROS accumulation facilitating melanogenesis.

A ReaxFF-based molecular dynamics study of the mechanisms of interactions between reactive oxygen plasma species and the Candida albicans cell wall

NASA Astrophysics Data System (ADS)

Zhao, T.; Shi, L.; Zhang, Y. T.; Zou, L.; Zhang, L.

2017-10-01

Atmospheric pressure non-equilibrium plasmas have attracted significant attention and have been widely used to inactivate pathogens, yet the mechanisms underlying the interactions between plasma-generated species and bio-organisms have not been elucidated clearly. In this paper, reactive molecular dynamics simulations are employed to investigate the mechanisms of interactions between reactive oxygen plasma species (O, OH, and O2) and β-1,6-glucan (a model for the C. albicans cell wall) from a microscopic point of view. Our simulations show that O and OH species can break structurally important C-C and C-O bonds, while O2 molecules exhibit only weak, non-bonded interactions with β-1,6-glucan. Hydrogen abstraction from hydroxyl or CH groups occurs first in all bond cleavage mechanisms. This is followed by a cascade of bond cleavage and double bond formation events. These lead to the destruction of the fungal cell wall. O and OH have similar effects related to their bond cleavage mechanisms. Our simulation results provide fundamental insights into the mechanisms underlying the interactions between reactive oxygen plasma species and the fungal cell wall of C. albicans at the atomic level.

Clear microstructure-performance relationships in Mn-containing perovskite and hexaaluminate compounds prepared by activated reactive synthesis.

PubMed

Laassiri, Said; Bion, Nicolas; Duprez, Daniel; Royer, Sébastien; Alamdari, Houshang

2014-03-07

Microstructural properties of mixed oxides play essential roles in their oxygen mobility and consequently in their catalytic performances. Two families of mixed oxides (perovskite and hexaaluminate) with different microstructural features, such as crystal size and specific surface area, were prepared using the activated reactive synthesis (ARS) method. It was shown that ARS is a flexible route to synthesize both mixed oxides with nano-scale crystal size and high specific surface area. Redox properties and oxygen mobility were found to be strongly affected by the material microstructure. Catalytic activities of hexaaluminate and perovskite materials for methane oxidation were discussed in the light of structural, redox and oxygen mobility properties.

Mapping the pharmacological modulation of brain oxygen metabolism: The effects of caffeine on absolute CMRO2 measured using dual calibrated fMRI.

PubMed

Merola, Alberto; Germuska, Michael A; Warnert, Esther Ah; Richmond, Lewys; Helme, Daniel; Khot, Sharmila; Murphy, Kevin; Rogers, Peter J; Hall, Judith E; Wise, Richard G

2017-07-15

This study aims to map the acute effects of caffeine ingestion on grey matter oxygen metabolism and haemodynamics with a novel MRI method. Sixteen healthy caffeine consumers (8 males, age=24.7±5.1) were recruited to this randomised, double-blind, placebo-controlled study. Each participant was scanned on two days before and after the delivery of an oral caffeine (250mg) or placebo capsule. Our measurements were obtained with a newly proposed estimation approach applied to data from a dual calibration fMRI experiment that uses hypercapnia and hyperoxia to modulate brain blood flow and oxygenation. Estimates were based on a forward model that describes analytically the contributions of cerebral blood flow (CBF) and of the measured end-tidal partial pressures of CO 2 and O 2 to the acquired dual-echo GRE signal. The method allows the estimation of grey matter maps of: oxygen extraction fraction (OEF), CBF, CBF-related cerebrovascular reactivity (CVR) and cerebral metabolic rate of oxygen consumption (CMRO 2 ). Other estimates from a multi inversion time ASL acquisition (mTI-ASL), salivary samples of the caffeine concentration and behavioural measurements are also reported. We observed significant differences between caffeine and placebo on average across grey matter, with OEF showing an increase of 15.6% (SEM±4.9%, p<0.05) with caffeine, while CBF and CMRO 2 showed differences of -30.4% (SEM±1.6%, p<0.01) and -18.6% (SEM±2.9%, p<0.01) respectively with caffeine administration. The reduction in oxygen metabolism found is somehow unexpected, but consistent with a hypothesis of decreased energetic demand, supported by previous electrophysiological studies reporting reductions in spectral power with EEG. Moreover the maps of the physiological parameters estimated illustrate the spatial distribution of changes across grey matter enabling us to localise the effects of caffeine with voxel-wise resolution. CBF changes were widespread as reported by previous findings, while changes in OEF were found to be more restricted, leading to unprecedented mapping of significant CMRO 2 reductions mainly in frontal gyrus, parietal and occipital lobes. In conclusion, we propose the estimation framework based on our novel forward model with a dual calibrated fMRI experiment as a viable MRI method to map the effects of drugs on brain oxygen metabolism and haemodynamics with voxel-wise resolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Reactive oxygen species generation in aqueous solutions containing GdVO4:Eu3+ nanoparticles and their complexes with methylene blue

NASA Astrophysics Data System (ADS)

Hubenko, Kateryna; Yefimova, Svetlana; Tkacheva, Tatyana; Maksimchuk, Pavel; Borovoy, Igor; Klochkov, Vladimir; Kavok, Nataliya; Opolonin, Oleksander; Malyukin, Yuri

2018-04-01

It this letter, we report the study of free radicals and reactive oxygen species (ROS) generation in water solutions containing gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) and their complexes with methylene blue (MB) photosensitizer. The catalytic activity was studied under UV-Vis and X-ray irradiation by three methods (conjugated dienes test, OH· radical, and singlet oxygen detection). It has been shown that the VNPs-MB complexes reveal high efficiency of ROS generation under UV-Vis irradiation associated with both high efficiency of OH· radicals generation by VNPs and singlet oxygen generation by MB due to nonradiative excitation energy transfer from VNPs to MB molecules. Contrary to that under X-ray irradiation, the strong OH . radicals scavenging by VNPs has been observed.

Reactive oxygen species generation in aqueous solutions containing GdVO4:Eu3+ nanoparticles and their complexes with methylene blue.

PubMed

Hubenko, Kateryna; Yefimova, Svetlana; Tkacheva, Tatyana; Maksimchuk, Pavel; Borovoy, Igor; Klochkov, Vladimir; Kavok, Nataliya; Opolonin, Oleksander; Malyukin, Yuri

2018-04-13

It this letter, we report the study of free radicals and reactive oxygen species (ROS) generation in water solutions containing gadolinium orthovanadate GdVO 4 :Eu 3+ nanoparticles (VNPs) and their complexes with methylene blue (MB) photosensitizer. The catalytic activity was studied under UV-Vis and X-ray irradiation by three methods (conjugated dienes test, OH· radical, and singlet oxygen detection). It has been shown that the VNPs-MB complexes reveal high efficiency of ROS generation under UV-Vis irradiation associated with both high efficiency of OH· radicals generation by VNPs and singlet oxygen generation by MB due to nonradiative excitation energy transfer from VNPs to MB molecules. Contrary to that under X-ray irradiation, the strong OH . radicals scavenging by VNPs has been observed.

Development of ITM Oxygen Technology for Low-cost and Low-emission Gasification and Other Industrial Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fogash, Kevin

2015-12-15

Air Products carried out a scope of work under DOE Award No. DE-FE0012065 “Development of ITM Oxygen Technology for Low-cost and Low-emission Gasification and Other Industrial Applications” with subcontractors Ceramatec, Penn State, and WorleyParsons. The scope of work under this award was aimed at furthering the development of the Ion Transport Membrane (ITM) Oxygen production process toward a demonstration-scale facility known as the Oxygen Development Facility (ODF). Specific activities will help to enable design and construction of the ODF through advancement of a number of challenging technical elements that are required to manage risk in the initial deployment of ITMmore » technology. Major objectives of the work included developing ITM Oxygen ceramic membrane materials with improved performance and reliability, optimizing ceramic module geometry and fabrication methods, testing module performance, trialing the improved fabrication process at commercial scale in the Ceramic Membrane Module Fabrication Facility (CerFab), and advancing engineering development of the ITM oxygen production process, including vessel design and contaminant control measures to prepare for deployment of the ODF. The comprehensive report that follows details the team’s work, which includes several notable accomplishments: 1) compressive creep, a likely limiter of ceramic module lifetime in service, was demonstrated to be retarded by an order of magnitude by changes in material formulation, module joining dimensions, and internal wafer geometry; 2) two promising new materials were shown to be superior to the incumbent ITM material in a key material parameter related to oxygen flux; 3) module degradation mechanisms were identified following operation in large pilot-scale equipment; 4) options for utilizing ITM in a coal-to-liquids (CTL) facility to enable liquids production with carbon capture were identified and studied; and 5) the benefits of potential improvements to the technology were assessed for their cost impact on ITM Oxygen applications to clean power, fuels, and other applications.« less

Development of ITM Oxygen Technology for Low-cost and Low-emission Gasification and Other Industrial Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fogash, Kevin

Air Products carried out a scope of work under DOE Award No. DE-FE0012065 “Development of ITM Oxygen Technology for Low-cost and Low-emission Gasification and Other Industrial Applications” with subcontractors Ceramatec, Penn State, and WorleyParsons. The scope of work under this award was aimed at furthering the development of the Ion Transport Membrane (ITM) Oxygen production process toward a demonstration-scale facility known as the Oxygen Development Facility (ODF). Specific activities will help to enable design and construction of the ODF through advancement of a number of challenging technical elements that are required to manage risk in the initial deployment of ITMmore » technology. Major objectives of the work included developing ITM Oxygen ceramic membrane materials with improved performance and reliability, optimizing ceramic module geometry and fabrication methods, testing module performance, trialing the improved fabrication process at commercial scale in the Ceramic Membrane Module Fabrication Facility (CerFab), and advancing engineering development of the ITM oxygen production process, including vessel design and contaminant control measures to prepare for deployment of the ODF. The comprehensive report that follows details the team’s work, which includes several notable accomplishments: 1) compressive creep, a likely limiter of ceramic module lifetime in service, was demonstrated to be retarded by an order of magnitude by changes in material formulation, module joining dimensions, and internal wafer geometry; 2) two promising new materials were shown to be superior to the incumbent ITM material in a key material parameter related to oxygen flux; 3) module degradation mechanisms were identified following operation in large pilot-scale equipment; 4) options for utilizing ITM in a coal-to-liquids (CTL) facility to enable liquids production with carbon capture were identified and studied; and 5) the benefits of potential improvements to the technology were assessed for their cost impact on ITM Oxygen applications to clean power, fuels, and other applications.« less

Olive leaf extracts protect cardiomyocytes against 4-hydroxynonenal-induced toxicity in vitro: comparison with oleuropein, hydroxytyrosol, and quercetin.

PubMed

Bali, Elif Burcu; Ergin, Volkan; Rackova, Lucia; Bayraktar, Oğuz; Küçükboyaci, Nurgün; Karasu, Çimen

2014-08-01

Olive (Olea europaea) leaf, an important traditional herbal medicine, displays cardioprotection that may be related to the cellular redox modulating effects of its polyphenolic constituents. This study was undertaken to investigate the protective effect of the ethanolic and methanolic extracts of olive leaves compared to the effects of oleuropein, hydroxytyrosol, and quercetin as a positive standard in a carbonyl compound (4-hydroxynonenal)-induced model of oxidative damage to rat cardiomyocytes (H9c2). Cell viability was detected by the MTT assay; reactive oxygen species production was assessed by the 2',7'-dichlorodihydrofluorescein diacetate method, and the mitochondrial membrane potential was determined using a JC-1 dye kit. Phospho-Hsp27 (Ser82), phospho-MAPKAPK-2 (Thr334), phospho-c-Jun (Ser73), cleaved-caspase-3 (cl-CASP3) (Asp175), and phospho-SAPK/JNK (Thr183/Tyr185) were measured by Western blotting. The ethanolic and methanolic extracts of olive leaves inhibited 4-hydroxynonenal-induced apoptosis, characterized by increased reactive oxygen species production, impaired viability (LD50: 25 µM), mitochondrial dysfunction, and activation of pro-apoptotic cl-CASP3. The ethanolic and methanolic extracts of olive leaves also inhibited 4-hydroxynonenal-induced phosphorylation of stress-activated transcription factors, and the effects of extracts on p-SAPK/JNK, p-Hsp27, and p-MAPKAPK-2 were found to be concentration-dependent and comparable with oleuropein, hydroxytyrosol, and quercetin. While the methanolic extract downregulated 4-hydroxynonenal-induced p-MAPKAPK-2 and p-c-Jun more than the ethanolic extract, it exerted a less inhibitory effect than the ethanolic extract on 4-hydroxynonenal-induced p-SAPK/JNK and p-Hsp27. cl-CASP3 and p-Hsp27 were attenuated, especially by quercetin. Experiments showed a predominant reactive oxygen species inhibitory and mitochondrial protecting ability at a concentration of 1-10 µg/mL of each extract, oleuropein, hydroxytyrosol, and quercetin. The ethanolic extract of olive leaves, which contains larger amounts of oleuropein, hydroxytyrosol, verbascoside, luteolin, and quercetin (by HPLC) than the methanolic one, has more protecting ability on cardiomyocyte viability than the methanolic extract or each phenolic compound against 4-hydroxynonenal-induced carbonyl stress and toxicity. Georg Thieme Verlag KG Stuttgart · New York.

Ligand-induced dynamics of heterotrimeric G protein-coupled receptor-like kinase complexes

DOE PAGES

Tunc-Ozdemir, Meral; Jones, Alan M.

2017-02-10

Background Arabidopsis, 7-transmembrane Regulator of G signaling protein 1 (AtRGS1) modulates canonical G protein signaling by promoting the inactive state of heterotrimeric G protein complex on the plasma membrane. It is known that plant leucine-rich repeat receptor-like kinases (LRR RLKs) phosphorylate AtRGS1 in vitro but little is known about the in vivo interaction, molecular dynamics, or the cellular consequences of this interaction. Methods Therefore, a subset of the known RLKs that phosphorylate AtRGS1 were selected for elucidation, namely, BAK1, BIR1, FLS2. Several microscopies for both static and dynamic protein-protein interactions were used to follow in vivo interactions between the RLKsmore » and AtRGS1 after the presentation of the Pathogen-associated Molecular Pattern, Flagellin 22 (Flg22). These microscopies included FoÈrster Resonance Energy Transfer, Bimolecular Fluoresence Complementation, and Cross Number and Brightness fluorescence Correlation Spectroscopy. In addition, reactive oxygen species and calcium changes in living cells were quantitated using luminometry and R-GECO1 microscopy. Results The LRR RLKs BAK1 and BIR1, interact with AtRGS1 at the plasma membrane. The RLK ligand flg22 sets BAK1 in motion toward AtRGS1 and BIR1 away, both returning to the baseline orientations by 10 minutes. The C-terminal tail of AtRGS1 is important for the interaction with BAK1 and for the tempo of the AtRGS1/BIR1 dynamics. This window of time corresponds to the flg22-induced transient production of reactive oxygen species and calcium release which are both attenuated in the rgs1 and the bak1 null mutants. Conclusions A temporal model of these interactions is proposed. flg22 binding induces nearly instantaneous dimerization between FLS2 and BAK1. Phosphorylated BAK1 interacts with and enables AtRGS1 to move away from BIR1 and AtRGS1 becomes phosphorylated leading to its endocytosis thus leading to de-repression by permitting AtGPA1 to exchange GDP for GTP. Finally, the G protein complex becomes dissociated thus AGB1 interacts with its effector proteins leading to changes in reactive oxygen species and calcium.« less

Ligand-induced dynamics of heterotrimeric G protein-coupled receptor-like kinase complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tunc-Ozdemir, Meral; Jones, Alan M.

Background Arabidopsis, 7-transmembrane Regulator of G signaling protein 1 (AtRGS1) modulates canonical G protein signaling by promoting the inactive state of heterotrimeric G protein complex on the plasma membrane. It is known that plant leucine-rich repeat receptor-like kinases (LRR RLKs) phosphorylate AtRGS1 in vitro but little is known about the in vivo interaction, molecular dynamics, or the cellular consequences of this interaction. Methods Therefore, a subset of the known RLKs that phosphorylate AtRGS1 were selected for elucidation, namely, BAK1, BIR1, FLS2. Several microscopies for both static and dynamic protein-protein interactions were used to follow in vivo interactions between the RLKsmore » and AtRGS1 after the presentation of the Pathogen-associated Molecular Pattern, Flagellin 22 (Flg22). These microscopies included FoÈrster Resonance Energy Transfer, Bimolecular Fluoresence Complementation, and Cross Number and Brightness fluorescence Correlation Spectroscopy. In addition, reactive oxygen species and calcium changes in living cells were quantitated using luminometry and R-GECO1 microscopy. Results The LRR RLKs BAK1 and BIR1, interact with AtRGS1 at the plasma membrane. The RLK ligand flg22 sets BAK1 in motion toward AtRGS1 and BIR1 away, both returning to the baseline orientations by 10 minutes. The C-terminal tail of AtRGS1 is important for the interaction with BAK1 and for the tempo of the AtRGS1/BIR1 dynamics. This window of time corresponds to the flg22-induced transient production of reactive oxygen species and calcium release which are both attenuated in the rgs1 and the bak1 null mutants. Conclusions A temporal model of these interactions is proposed. flg22 binding induces nearly instantaneous dimerization between FLS2 and BAK1. Phosphorylated BAK1 interacts with and enables AtRGS1 to move away from BIR1 and AtRGS1 becomes phosphorylated leading to its endocytosis thus leading to de-repression by permitting AtGPA1 to exchange GDP for GTP. Finally, the G protein complex becomes dissociated thus AGB1 interacts with its effector proteins leading to changes in reactive oxygen species and calcium.« less

Probing ‘Spin-Forbidden’ Oxygen Atom Transfer: Gas-Phase Reactions of Chromium-Porphyrin Complexes

PubMed Central

Fornarini, Simonetta; Lanucara, Francesco; Warren, Jeffrey J.

2010-01-01

Oxygen-atom transfer reactions of metalloporphyrin species play an important role in biochemical and synthetic oxidation reactions. An emerging theme in this chemistry is that spin-state changes can play important roles, and a ‘two-state’ reactivity model has been extensively applied especially in iron-porphyrin systems. Herein we explore the gas phase oxygen-atom transfer chemistry of meso-tetrakis(pentafluorophenyl)porphyrin (TPFPP) chromium complexes, as well as some other tetradentate macrocyclic ligands. Electrospray ionization in concert with Fourier transform ion cyclotron resonance (FT-ICR) spectrometry has been used to characterize and observe reactivity of the ionic species [(TPFPP)CrIII]+ (1) and [(TPFPP)CrVO]+ (2). These are an attractive system to examine the effects of spin state change on oxygen atom transfer because the d1 CrV species are doublets while the CrIII complexes have quartet ground states with high-lying doublet excited states. In the gas phase, [(TPFPP)CrIII]+ forms adducts with a variety of neutral donors but O-atom transfer is only observed for NO2. Pyridine N-oxide adducts of 1 do yield 2 upon collision induced dissociation (CID), but the ethylene oxide, DMSO, and TEMPO analogs do not. [(TPFPP)CrVO]+ is shown by its reactivity and by CID experiments to be a terminal metal-oxo with a single vacant coordination site. It also displays limited reaction chemistry, being deoxygenated only by the very potent reductant P(OMe)3. In general, [(TPFPP)CrVO]+ species are much less reactive than the Fe and Mn analogs. Thermochemical analysis of the reactions points towards the involvement of spin issues in the lower observed reactivity of the chromium complexes. PMID:20218631

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

PubMed

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

2017-03-15

We studied whether the β 1 -adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O 2 - ) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H 2 O 2 ) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Nox1, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxo1), c-Src, p47 phox or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) Cδ and Rac1. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKCδ and Rac1, which are important activators of NADPH oxidase. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamics, Stability, and Adsorption States of Water on Oxidized RuO 2 (110)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Manh-Thuong; Mu, Rentao; Cantu, David C.

Identifying and understanding how excess oxygen atoms affect the adsorption of water on metal oxides is crucial for their use in water splitting. Here, by means of high-resolution scanning tunneling microscopy and density-functional calculations, we show that excess oxygen atoms on the stoichiometric RuO2(110) significantly change the clustering, conformation, and deprotonation equilibrium of adsorbed water. We considered two reactive scenarios during which the stoichiometric surface was exposed to: (i) first to oxygen followed by water, and (ii) first to water followed by oxygen. In both cases the [OH-OH] complex on Ru rows is the dominant species, showing a significant differencemore » from water-only adsorption on the stoichiometric surface in which the [OH-H2O] species is found to be prevalent. Surface reactivity at almost full O coverage is also addressed; there we show that site selectivity of the surface for H adsorption and dissociation of H2O is hindered, notwithstanding the increase of the dynamical motion of both species. We found that the work function of RuO2 can serve as a descriptor for the reactivity of this surface to water and its constituents.« less

Endocellular regulation by free radicals and hydrogen peroxide: key determinants of the inflammatory response.

PubMed

Vitetta, Luis; Linnane, Anthony W

2014-04-01

The formations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been considered as major contributors to the dysregulation of the inflammatory response. Reactive oxygen species and RNS productions often are reported to be associated with the development of chronic diseases and acceleration of the aging process. Mechanistically, this association has linked the phenomena of oxidative stress with the occurrence of random deleterious modifications of macromolecules with progressive development of pro-inflammatory conditions promoting age-associated systemic diseases. On the contrary the so-called random modification of macromolecules is incorrect rather ROS and RNS are molecular regulators (second messengers) and not universal toxins whose overproduction should be annulled by antioxidants. We have previously reviewed the physiological role of superoxide anion (and hydrogen peroxide) and nitric oxide (and peroxynitrite) and concluded that these reactive molecular species behave as pro-oxidant second messengers. Reactive oxygen species and RNS are produced at specific cellular locations and are essential for both the normal physiological function of the metabolome and the regulated inflammatory response. This brings into question the whole concept of the orally administering of antioxidant molecular species to down-regulate or abrogate an overproduction of free radical activity. There are no human clinical trials that demonstrate that small molecules, the so-called antioxidants (e.g., vitamins C, vitamin E and beta-carotene), confer a favorable clinical outcome of long-lasting control of inflammation.

Correlation Between High-sensitivity C-reactive Protein and Reactive Oxygen Metabolites During A One-year Period Among Asymptomatic Subjects

PubMed Central

Kotani, Kazuhiko; Taniguchi, Nobuyuki

2012-01-01

Background Inflammation and oxidative stress are associated with human health and the disease status. The present study aimed to investigate the longitudinal correlation between the diacron reactive oxygen metabolites (d-ROMs) level, as an oxidative stress-related marker, and high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, during a one-year period among asymptomatic subjects. Methods The data, including anthropometric and biochemical markers, were collected at baseline and after the one-year period from 71 participants (male/female = 41/30, mean age 50 years). The correlation between the changes of the d-ROMs and hsCRP levels during the study period was examined. Results A simple correlation analysis showed a significant and positive correlation to exist between the changes of the d-ROMs and hsCRP levels (r = 0.40, P < 0.01). This significant correlation remained independent in a multiple linear regression analysis adjusted for confounding factors. Conclusions The present findings suggest that the relationship between the d-ROMs and hsCRP levels could be prospectively followed, and that monitoring both markers may help to better understand the cooperation of inflammation and oxidative stress in association with health and disease. Further studies are necessary to clarify the biological mechanism(s) responsible for the observed relationship. Keywords Oxidative stress; Oxygen reactive species; Inflammation; CRP PMID:22383928

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma

PubMed Central

Singer, E; Judkins, J; Salomonis, N; Matlaf, L; Soteropoulos, P; McAllister, S; Soroceanu, L

2015-01-01

Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN–MES transition. This ‘reprogramming' of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM. PMID:25590811

Manganoporphyrin-Polyphenol Multilayer Capsules as Radical and Reactive Oxygen Species (ROS) Scavengers

DOE PAGES

Alford, Aaron; Kozlovskaya, Veronika; Xue, Bing; ...

2017-12-18

Local modulation of oxidative stress is crucial for a variety of biochemical events including cellular differentiation, apoptosis, and defense against pathogens. Currently employed natural and synthetic antioxidants exhibit a lack of biocompatibility, bioavailability, and chemical stability, resulting in limited capability to scavenge reactive oxygen species (ROS). To mediate these drawbacks, we have developed a synergistic manganoporphyrin-polyphenol polymeric nanothin coating and hollow microcapsules with efficient antioxidant activity and controllable ROS modulation. These materials are produced by multilayer assembly of a natural polyphenolic antioxidant, tannic acid (TA), with a synthesized copolymer of polyvinylpyrrolidone containing a manganoporphyrin modality (MnP-PVPON) which mimics the enzymaticmore » antioxidant superoxide dismutase. The redox activity of the copolymer is demonstrated to dramatically increase the antioxidant response of MnP-PVPON/TA capsules versus unmodified PVPON/TA capsules through reduction of a radical cationic dye and to significantly suppress the proliferation of superoxide via cytochrome C competition. Inclusion of MnP-PVPON as an outer layer enhances radical-scavenging activity as compared to localization of the layer in the middle or inner part of the capsule shell. In addition, we demonstrate that TA is crucial for the synergistic radical-scavenging activity of the MnP-PVPON/TA system which exhibits a combined superoxide dismutase-like ability and catalase-like activity in response to the free radical superoxide challenge. The MnP-PVPON/TA capsules exhibit a negligible, 8% loss of shell thickness upon free radical treatment, while PVPON/TA capsules lose 39% of their shell thickness due to the noncatalytic free-radical-scavenging of TA, as demonstrated by small angle neutron scattering (SANS). Finally, we have found the manganoporphyrin-polyphenol capsules to be nontoxic to splenocytes from NOD mice after 48 h incubation. In conclusion, our study illustrates the strong potential of combining catalytic activity of manganoporphyrins with natural polyphenolic antioxidants to design efficient free-radical-scavenging materials that may eventually be used in antioxidant therapies and as free radical dissipating protective carriers of biomolecules for biomedical or industrial applications.« less

Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bumpus, Namandje N., E-mail: nbumpus1@jhmi.edu

Chronic use of efavirenz (EFV) has been linked to incidences of hepatotoxicity in patients receiving EFV to treat HIV-1. While recent studies have demonstrated that EFV stimulates hepatic cell death a role for the metabolites of efavirenz in this process has yet to be examined. In the present study, incubation of primary human hepatocytes with synthetic 8-hydroxyEFV (8-OHEFV), which is the primary metabolite of EFV, resulted in cell death, caspase-3 activation and reactive oxygen species formation. The metabolite exerted these effects at earlier time points and using lower concentrations than were required for the parent compound. In addition, pharmacological inhibitionmore » of cytochrome P450-dependent metabolism of EFV using 1-aminobenzotriazole markedly decreased reactive oxygen species formation and cell death. Treatment of primary human hepatocytes with EFV and 8-OHEFV also stimulated phosphorylation of c-Jun N-terminal kinase (JNK) as well as phosphorylation of the JNK substrate c-Jun. Further, the mRNA and protein expression of an isoform of Bim (Bcl-2 interacting mediator of cell death) denoted as BimEL, which is proapoptotic and has been shown to be modulated by JNK, was increased. Inhibition of JNK using SP600125 prevented the EFV- and 8-OHEFV-mediated cell death. Silencing of Bim using siRNA transfected into hepatocytes also prevented cell death resulting from 8-OHEFV-treatment. These data suggest that the oxidative metabolite 8-OHEFV is a more potent inducer of hepatic cell death than the parent compound EFV. Further, activation of the JNK signaling pathway and BimEL mRNA expression appear to be required for EFV- and 8-OHEFV-mediated hepatocyte death. -- Highlights: Black-Right-Pointing-Pointer 8-Hydroxyefavirenz is a more potent stimulator of cell death than efavirenz. Black-Right-Pointing-Pointer Efavirenz and 8-hydroxyefavirenz increase JNK activity and BimEL mRNA expression. Black-Right-Pointing-Pointer JNK and Bim are required for efavirenz- and 8-hydroxyefavirenz-mediated cell death. Black-Right-Pointing-Pointer Efavirenz and 8-hydroxyefavirenz may be novel modulators of Bim.« less

Manganoporphyrin-Polyphenol Multilayer Capsules as Radical and Reactive Oxygen Species (ROS) Scavengers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alford, Aaron; Kozlovskaya, Veronika; Xue, Bing

Local modulation of oxidative stress is crucial for a variety of biochemical events including cellular differentiation, apoptosis, and defense against pathogens. Currently employed natural and synthetic antioxidants exhibit a lack of biocompatibility, bioavailability, and chemical stability, resulting in limited capability to scavenge reactive oxygen species (ROS). To mediate these drawbacks, we have developed a synergistic manganoporphyrin-polyphenol polymeric nanothin coating and hollow microcapsules with efficient antioxidant activity and controllable ROS modulation. These materials are produced by multilayer assembly of a natural polyphenolic antioxidant, tannic acid (TA), with a synthesized copolymer of polyvinylpyrrolidone containing a manganoporphyrin modality (MnP-PVPON) which mimics the enzymaticmore » antioxidant superoxide dismutase. The redox activity of the copolymer is demonstrated to dramatically increase the antioxidant response of MnP-PVPON/TA capsules versus unmodified PVPON/TA capsules through reduction of a radical cationic dye and to significantly suppress the proliferation of superoxide via cytochrome C competition. Inclusion of MnP-PVPON as an outer layer enhances radical-scavenging activity as compared to localization of the layer in the middle or inner part of the capsule shell. In addition, we demonstrate that TA is crucial for the synergistic radical-scavenging activity of the MnP-PVPON/TA system which exhibits a combined superoxide dismutase-like ability and catalase-like activity in response to the free radical superoxide challenge. The MnP-PVPON/TA capsules exhibit a negligible, 8% loss of shell thickness upon free radical treatment, while PVPON/TA capsules lose 39% of their shell thickness due to the noncatalytic free-radical-scavenging of TA, as demonstrated by small angle neutron scattering (SANS). Finally, we have found the manganoporphyrin-polyphenol capsules to be nontoxic to splenocytes from NOD mice after 48 h incubation. In conclusion, our study illustrates the strong potential of combining catalytic activity of manganoporphyrins with natural polyphenolic antioxidants to design efficient free-radical-scavenging materials that may eventually be used in antioxidant therapies and as free radical dissipating protective carriers of biomolecules for biomedical or industrial applications.« less