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Sample records for oxide inhibits capacitative

  1. Capacitive behavior of highly-oxidized graphite

    NASA Astrophysics Data System (ADS)

    Ciszewski, Mateusz; Mianowski, Andrzej

    2014-09-01

    Capacitive behavior of a highly-oxidized graphite is presented in this paper. The graphite oxide was synthesized using an oxidizing mixture of potassium chlorate and concentrated fuming nitric acid. As-oxidized graphite was quantitatively and qualitatively analyzed with respect to the oxygen content and the species of oxygen-containing groups. Electrochemical measurements were performed in a two-electrode symmetric cell using KOH electrolyte. It was shown that prolonged oxidation causes an increase in the oxygen content while the interlayer distance remains constant. Specific capacitance increased with oxygen content in the electrode as a result of pseudo-capacitive effects, from 0.47 to 0.54 F/g for a scan rate of 20 mV/s and 0.67 to 1.15 F/g for a scan rate of 5 mV/s. Better cyclability was observed for the electrode with a higher oxygen amount.

  2. Material characteristics and equivalent circuit models of stacked graphene oxide for capacitive humidity sensors

    NASA Astrophysics Data System (ADS)

    Han, Kook In; Kim, Seung Du; Yang, Woo Seok; Kim, Hyeong Seok; Shin, Myunghun; Kim, Jong Pil; Lee, In Gyu; Cho, Byung Jin; Hwang, Wan Sik

    2016-03-01

    The oxidation properties of graphene oxide (GO) are systematically correlated with their chemical sensing properties. Based on an impedance analysis, the equivalent circuit models of the capacitive sensors are established, and it is demonstrated that capacitive operations are related to the degree of oxidation. This is also confirmed by X-ray diffraction and Raman analysis. Finally, highly sensitive stacked GO sensors are shown to detect humidity in capacitive mode, which can be useful in various applications requiring low power consumption.

  3. Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?

    PubMed Central

    Aitken, Robert J; Baker, Mark A; Nixon, Brett

    2015-01-01

    This chapter explores the possibility that capacitation and apoptosis are linked processes joined by their common dependence on the continued generation of reactive oxygen species (ROS). According to this model capacitation is initiated in spematozoa following their release into the female reproductive tract as a consequence of intracellular ROS generation, which stimulates intracellular cAMP generation, inhibits tyrosine phosphatase activity and enhances the formation of oxysterols prior to their removal from the sperm surface by albumin. The continued generation of ROS by capacitating populations of spermatozoa eventually overwhelms the limited capacity of these cells to protect themselves from oxidative stress. As a result the over-capacitation of spermatozoa leads to a state of senescence and the activation of a truncated intrinsic apoptotic cascade characterized by enhanced mitochondrial ROS generation, lipid peroxidation, motility loss, caspase activation and phosphatidylserine externalization. The latter may be particularly important in instructing phagocytic leukocytes that the removal of senescent, moribund spermatozoa should be a silent process unaccompanied by the generation of proinflammatory cytokines. These observations reveal the central role played by redox chemistry in defining the life and death of spermatozoa. A knowledge of these mechanisms may help us to engineer novel solutions to both support and preserve the functionality of these highly specialized cells. PMID:25999358

  4. Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress?

    PubMed

    Aitken, Robert J; Baker, Mark A; Nixon, Brett

    2015-01-01

    This chapter explores the possibility that capacitation and apoptosis are linked processes joined by their common dependence on the continued generation of reactive oxygen species (ROS). According to this model capacitation is initiated in spematozoa following their release into the female reproductive tract as a consequence of intracellular ROS generation, which stimulates intracellular cAMP generation, inhibits tyrosine phosphatase activity and enhances the formation of oxysterols prior to their removal from the sperm surface by albumin. The continued generation of ROS by capacitating populations of spermatozoa eventually overwhelms the limited capacity of these cells to protect themselves from oxidative stress. As a result the over-capacitation of spermatozoa leads to a state of senescence and the activation of a truncated intrinsic apoptotic cascade characterized by enhanced mitochondrial ROS generation, lipid peroxidation, motility loss, caspase activation and phosphatidylserine externalization. The latter may be particularly important in instructing phagocytic leukocytes that the removal of senescent, moribund spermatozoa should be a silent process unaccompanied by the generation of proinflammatory cytokines. These observations reveal the central role played by redox chemistry in defining the life and death of spermatozoa. A knowledge of these mechanisms may help us to engineer novel solutions to both support and preserve the functionality of these highly specialized cells.

  5. Anodized aluminum oxide-based capacitance sensors for the direct detection of DNA hybridization.

    PubMed

    Kang, Bongkeun; Yeo, Unjin; Yoo, Kyung-Hwa

    2010-03-15

    We fabricated a capacitance sensor based on an anodized aluminum oxide (AAO) nanoporous structure to detect DNA hybridization. We utilized Au film deposited on the surface of the AAO membrane and Au nanowires infiltrating the nanopores as the top and bottom electrodes, respectively. When completely complementary target DNA molecules were added to the sensor-immobilized DNA molecule probes, the capacitance was reduced; with a concentration of 1pM, the capacitance decreased by approximately 10%. We measured the capacitance change for different concentrations of the target DNA solution. A linear relationship was found between the capacitance change and DNA concentration on a semi-logarithmic scale. We also investigated the possibility of detecting DNA molecules with a single-base mismatch to the probe DNA molecule. In contrast to complementary target DNA molecules, the addition of one-base mismatch DNA molecules caused no significant change in capacitance, demonstrating that DNA hybridization was detected with single nucleotide polymorphism sensitivity.

  6. Influence of surface oxidation on ion dynamics and capacitance in porous and nonporous carbon electrodes

    DOE PAGES

    Dyatkin, Boris; Zhang, Yu; Mamontov, Eugene; ...

    2016-04-07

    Here, we investigate the influence of surface chemistry and ion confinement on capacitance and electrosorption dynamics of room-temperature ionic liquids (RTILs) in supercapacitors. Using air oxidation and vacuum annealing, we produced defunctionalized and oxygen-rich surfaces of carbide-derived carbons (CDCs) and graphene nanoplatelets (GNPs). While oxidized surfaces of porous CDCs improve capacitance and rate handling abilities of ions, defunctionalized nonporous GNPs improve charge storage densities on planar electrodes. Quasi-elastic neutron scattering (QENS) and inelastic neutron scattering (INS) probed the structure, dynamics, and orientation of RTIL ions confined in divergently functionalized pores. Oxidized, ionophilic surfaces draw ions closer to pore surfaces andmore » enhance potential-driven ion transport during electrosorption. Molecular dynamics (MD) simulations corroborated experimental data and demonstrated the significance of surface functional groups on ion orientations, accumulation densities, and capacitance.« less

  7. Influence of surface oxidation on ion dynamics and capacitance in porous and nonporous carbon electrodes

    SciTech Connect

    Dyatkin, Boris; Zhang, Yu; Mamontov, Eugene; Kolesnikov, Alexander I.; Cheng, Yongqiang; Meyer, III, Harry M.; Cummings, Peter T.; Gogotsi, Yury G.

    2016-04-07

    Here, we investigate the influence of surface chemistry and ion confinement on capacitance and electrosorption dynamics of room-temperature ionic liquids (RTILs) in supercapacitors. Using air oxidation and vacuum annealing, we produced defunctionalized and oxygen-rich surfaces of carbide-derived carbons (CDCs) and graphene nanoplatelets (GNPs). While oxidized surfaces of porous CDCs improve capacitance and rate handling abilities of ions, defunctionalized nonporous GNPs improve charge storage densities on planar electrodes. Quasi-elastic neutron scattering (QENS) and inelastic neutron scattering (INS) probed the structure, dynamics, and orientation of RTIL ions confined in divergently functionalized pores. Oxidized, ionophilic surfaces draw ions closer to pore surfaces and enhance potential-driven ion transport during electrosorption. Molecular dynamics (MD) simulations corroborated experimental data and demonstrated the significance of surface functional groups on ion orientations, accumulation densities, and capacitance.

  8. Effect of reducing system on capacitive behavior of reduced graphene oxide film: Application for supercapacitor

    SciTech Connect

    Akbi, Hamdane; Yu, Lei; Wang, Bin; Liu, Qi; Wang, Jun; Liu, Jingyuan; Song, Dalei; Sun, Yanbo; Liu, Lianhe

    2015-01-15

    To determine the best chemical reduction of graphene oxide film with hydriodic acid that gives maximum energy and power density, we studied the effect of two reducing systems, hydriodic acid/water and hydriodic acid/acetic acid, on the morphology and electrochemical features of reduced graphene oxide film. Using acetic acid as solvent results in high electrical conductivity (5195 S m{sup −1}), excellent specific capacitance (384 F g{sup −1}) and good cyclic stability (about 98% of its initial response after 4000 cycles). Using water as a solvent, results in an ideal capacitive behavior and excellent cyclic stability (about 6% increase of its initial response after 2100 cycles). - Graphical abstract: The choice of reducing system determines the morphology and structure of the chemically reduced graphene film and, as a result, affects largely the capacitive behavior. - Highlights: • The structure of the graphene film has a pronounced effect on capacitive behavior. • The use of water/HI as reducing system results in an ideal capacitive behavior. • The use of acetic acid/HI as reducing system results in a high specific capacitance.

  9. Enhanced specific capacitance of modified needle cokes by controlling oxidation treatment

    NASA Astrophysics Data System (ADS)

    Yang, Sunhye; Kim, Ick-Jun; Choi, In-Sik; Kim, Hyun Soo; Tack Kim, Yu

    2010-05-01

    The electric double-layer performance of needle cokes can be affected by the morphology of structures. Hence, we introduce modified needle cokes by using simple oxidation treatment. The degree of graphitization with high specific capacitance is controlled by acid and heat treatment. The active sites of cokes are increased with increasing oxidation time. Dilute nitric acid (HNO3) and sodium chlorate (NaClO3) are used for the activation of cokes. In this case, the interlayer distance is dramatically increased from 3.5 to 8.9 Å. The specific capacitances are 33 F g-1 and 30 F ml-1, respectively, on a two-electrode system with a potential range of 0-2.5 V. The behaviors of double-layer capacitance are demonstrated by the charge-discharge process and the morphologies of modified needle cokes are analyzed by XRD, FE-SEM, BET and elemental analysis.

  10. Electrochemical and Capacitive Properties of Carbon Dots/Reduced Graphene Oxide Supercapacitors

    PubMed Central

    Dang, Yong-Qiang; Ren, Shao-Zhao; Liu, Guoyang; Cai, Jiangtao; Zhang, Yating; Qiu, Jieshan

    2016-01-01

    There is much recent interest in graphene-based composite electrode materials because of their excellent mechanical strengths, high electron mobilities, and large specific surface areas. These materials are good candidates for applications in supercapacitors. In this work, a new graphene-based electrode material for supercapacitors was fabricated by anchoring carbon dots (CDs) on reduced graphene oxide (rGO). The capacitive properties of electrodes in aqueous electrolytes were systematically studied by galvanostatic charge-discharge measurements, cyclic voltammetry, and electrochemical impedance spectroscopy. The capacitance of rGO was improved when an appropriate amount of CDs were added to the material. The CD/rGO electrode exhibited a good reversibility, excellent rate capability, fast charge transfer, and high specific capacitance in 1 M H2SO4. Its capacitance was as high as 211.9 F/g at a current density of 0.5 A/g. This capacitance was 74.3% higher than that of a pristine rGO electrode (121.6 F/g), and the capacitance of the CD/rGO electrode retained 92.8% of its original value after 1000 cycles at a CDs-to-rGO ratio of 5:1. PMID:28335339

  11. Facile labelling of graphene oxide for superior capacitive energy storage and fluorescence applications.

    PubMed

    Eng, Alex Yong Sheng; Chua, Chun Kiang; Pumera, Martin

    2016-04-14

    The majority of supercapacitor research studies on graphene materials today have been based upon developing electrochemical double-layer capacitors (EDLCs) using reduced graphenes. In contrast, graphene oxide (GO) is often neglected as a supercapacitor candidate due to its low electrical conductivity and surface area. Nonetheless, we present herein a fast (1 h) labelling of GO with o-phenylenediamine (PD) to produce PD-GO, exploiting inherent oxygen groups in creating new functionalities that exhibit capacitive enhancement from pseudo-capacitance. A high specific capacitance of 191 F g(-1) was obtained (at 0.2 A g(-1)), comparable to recent binder-free graphene supercapacitors. The large surface-normalized capacitance of up to 628 μF cm(-2) is also many times greater than the intrinsic capacitance of single-layer graphene (21 μF cm(-2)) as a result of additional pseudo-capacitance. A high capacity retention of ∼85% with each 10-fold increase in current density further indicates excellent rate performance. Hence, this approach in enhancing GO pseudo-capacitance may be similarly feasible as graphene EDLCs. Additionally, PD-GO was also found to exhibit a bright green fluorescence with a 540 nm maximum. The strongest fluorescence intensities arose from the smallest PD-GO fragments, and we attribute the origin to localised sp(2) domains and newly formed phenazine edge groups. The dual enhancement of dissimilar properties such as capacitance and fluorescence emphasizes the continued significance of covalent functionalisation towards tuning of properties in graphene-type materials.

  12. Nickel oxide film with open macropores fabricated by surfactant-assisted anodic deposition for high capacitance supercapacitors.

    PubMed

    Wu, Mao-Sung; Wang, Min-Jyle

    2010-10-07

    Nickel oxide film with open macropores prepared by anodic deposition in the presence of surfactant shows a very high capacitance of 1110 F g(-1) at a scan rate of 10 mV s(-1), and the capacitance value reduces to 950 F g(-1) at a high scan rate of 200 mV s(-1).

  13. Nanocellulose coupled flexible polypyrrole@graphene oxide composite paper electrodes with high volumetric capacitance

    NASA Astrophysics Data System (ADS)

    Wang, Zhaohui; Tammela, Petter; Strømme, Maria; Nyholm, Leif

    2015-02-01

    A robust and compact freestanding conducting polymer-based electrode material based on nanocellulose coupled polypyrrole@graphene oxide paper is straightforwardly prepared via in situ polymerization for use in high-performance paper-based charge storage devices, exhibiting stable cycling over 16 000 cycles at 5 A g-1 as well as the largest specific volumetric capacitance (198 F cm-3) so far reported for flexible polymer-based electrodes.A robust and compact freestanding conducting polymer-based electrode material based on nanocellulose coupled polypyrrole@graphene oxide paper is straightforwardly prepared via in situ polymerization for use in high-performance paper-based charge storage devices, exhibiting stable cycling over 16 000 cycles at 5 A g-1 as well as the largest specific volumetric capacitance (198 F cm-3) so far reported for flexible polymer-based electrodes. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07251k

  14. Gate tunneling current and quantum capacitance in metal-oxide-semiconductor devices with graphene gate electrodes

    NASA Astrophysics Data System (ADS)

    An, Yanbin; Shekhawat, Aniruddh; Behnam, Ashkan; Pop, Eric; Ural, Ant

    2016-11-01

    Metal-oxide-semiconductor (MOS) devices with graphene as the metal gate electrode, silicon dioxide with thicknesses ranging from 5 to 20 nm as the dielectric, and p-type silicon as the semiconductor are fabricated and characterized. It is found that Fowler-Nordheim (F-N) tunneling dominates the gate tunneling current in these devices for oxide thicknesses of 10 nm and larger, whereas for devices with 5 nm oxide, direct tunneling starts to play a role in determining the total gate current. Furthermore, the temperature dependences of the F-N tunneling current for the 10 nm devices are characterized in the temperature range 77-300 K. The F-N coefficients and the effective tunneling barrier height are extracted as a function of temperature. It is found that the effective barrier height decreases with increasing temperature, which is in agreement with the results previously reported for conventional MOS devices with polysilicon or metal gate electrodes. In addition, high frequency capacitance-voltage measurements of these MOS devices are performed, which depict a local capacitance minimum under accumulation for thin oxides. By analyzing the data using numerical calculations based on the modified density of states of graphene in the presence of charged impurities, it is shown that this local minimum is due to the contribution of the quantum capacitance of graphene. Finally, the workfunction of the graphene gate electrode is extracted by determining the flat-band voltage as a function of oxide thickness. These results show that graphene is a promising candidate as the gate electrode in metal-oxide-semiconductor devices.

  15. Reduced graphene oxide hydrogels deposited in nickel foam for supercapacitor applications: Toward high volumetric capacitance

    SciTech Connect

    Pham, Viet Hung; Dickerson, James H.

    2016-02-21

    Graphene hydrogels have been considered as ideal materials for high-performance supercapacitors. However, their low volumetric capacitance significantly limits its real application. In this study, we report an environment-friendly and scalable method to prepare high packing density, electrochemically reduced graphene oxide hydrogels (ERGO) for supercapacitor application by the electrophoretic deposition of graphene oxide onto nickel foam, followed by the electrochemical reduction and hydraulic compression of the deposited materials. The as-prepared ERGO on nickel foam was hydraulic compressed up to 20 tons, resulting in an increase of the packing density of ERGO from 0.0098 to 1.32 g cm–3. Consequently, the volumetric capacitance and volumetric energy density of ERGOs greatly increased from 1.58 F cm–3 and 0.053 Wh cm–3 (as-prepared ERGO) to 176.5 F cm–3 and 6.02 Wh cm–3 (ERGO compressed at 20 tons), respectively. The ERGOs also exhibited long-term electrochemical stability with a capacitance retention in the range of approximately 79–90% after 10 000 cycles. Lastly, we believe that these high packing density ERGOs are promising for real-world energy storage devices for which scalable, cost-effective manufacturing is of significance and for which space constraints are paramount.

  16. Electrochemical capacitance of iron oxide nanotube (Fe-NT): effect of annealing atmospheres.

    PubMed

    Sarma, Biplab; Jurovitzki, Abraham L; Ray, Rupashree S; Smith, York R; Mohanty, Swomitra K; Misra, Mano

    2015-07-03

    The effect of annealing atmosphere on the supercapacitance behavior of iron oxide nanotube (Fe-NT) electrodes has been explored and reported here. Iron oxide nanotubes were synthesized on a pure iron substrate through an electrochemical anodization process in an ethylene glycol solution containing 3% H2O and 0.5 wt.% NH4F. Subsequently, the annealing of the nanotubes was carried out at 500 °C for 2 h in various gas atmospheres such as air, oxygen (O2), nitrogen (N2), and argon (Ar). The morphology and crystal phases evolved after the annealing processes were examined via field emission scanning electron microscopy, x-ray diffraction, Raman spectroscopy, and x-ray photoelectron spectroscopy. The electrochemical capacitance properties of the annealed Fe-NT electrodes were evaluated by conducting cyclic voltammetry (CV), galvanostatic charge-discharge, and electrochemical impedance spectroscopy tests in the Li2SO4 electrolyte. Based on these experiments, it was found that the capacitance of the Fe-NT electrodes annealed in air and O2 atmospheres shows mixed behavior comprising both the electric double layer and pseudocapacitance. However, annealing in N2 and Ar environments resulted in well-defined redox peaks in the CV profiles of the Fe-NT electrodes, which are therefore attributed to the relatively higher pseudonature of the capacitance in these electrodes. Based on the galvanostatic charge-discharge studies, the specific capacitance achieved in the Fe-NT electrode after annealing in Ar was about 300 mF cm(-2), which was about twice the value obtained for N2-annealed Fe-NTs and three times higher than those annealed in air and O2. The experiments also demonstrated excellent cycle stability for the Fe-NT electrodes with 83%-85% capacitance retention, even after many charge-discharge cycles, irrespective of the gas atmospheres used during annealing. The increase in the specific capacitance was discussed in terms of increased oxygen vacancies as a result of the

  17. Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin.

    PubMed Central

    Moneer, Zahid; Dyer, Jeanette L; Taylor, Colin W

    2003-01-01

    In A7r5 vascular smooth muscle cells vasopressin, via arachidonic acid, regulates two Ca(2+)-entry pathways. Capacitative Ca(2+) entry (CCE), activated by empty Ca(2+) stores, is inhibited by arachidonic acid, and non-capacitative Ca(2+) entry (NCCE) is stimulated by it. This reciprocal regulation ensures that all Ca(2+) entry is via NCCE in the presence of vasopressin, while CCE mediates a transient Ca(2+) entry only after removal of vasopressin. We demonstrate that type III NO synthase (NOS III) is expressed in A7r5 cells and that NO inhibits CCE. Inhibition of CCE by vasopressin requires NOS III and the requirement lies downstream of arachidonic acid. Activation of soluble guanylate cyclase by NO and subsequent activation of protein kinase G are required for inhibition of CCE. Stimulation of NCCE by vasopressin also requires NOS III, but the stimulation is neither mimicked by cGMP nor blocked by inhibitors of soluble guanylate cyclase or protein kinase G. We conclude that arachidonic acid formed in response to vasopressin stimulates NOS III. NO then directly stimulates Ca(2+) entry through NCCE and, via protein kinase G, it inhibits CCE. The additional amplification provided by the involvement of guanylate cyclase and protein kinase G ensures that CCE will always be inhibited when vasopressin activates NCCE. PMID:12459038

  18. Sb-mediated Ge quantum dots in Ti-oxide-Si diode: negative differential capacitance.

    PubMed

    Rangel-Kuoppa, Victor-Tapio; Tonkikh, Alexander; Werner, Peter; Jantsch, Wolfgang

    2013-06-01

    The negative differential capacitance (NDC) effect is observed on a titanium-oxide-silicon structure, formed on n-type silicon with embedded germanium quantum dots (QDs). The Ge QDs were grown by an Sb-mediated technique. The NDC effect was observed for temperatures below 200 K. We found that approximately six to eight electrons can be trapped in the valence band states of Ge QDs. We explain the NDC effect in terms of the emission of electrons from valence band states in the very narrow QD layer under reverse bias.

  19. Index-matched indium tin oxide electrodes for capacitive touch screen panel applications.

    PubMed

    Hong, Chan-Hwa; Shin, Jae-Heon; Ju, Byeong-Kwon; Kim, Kyung-Hyun; Park, Nae-Man; Kim, Bo-Sul; Cheong, Woo-Seok

    2013-11-01

    Index-matched indium tin oxide (ITO) electrodes for capacitive touch screen panels have been fabricated to improve optical transmittance and reduce the difference of reflectance (deltaR) between the etched and un-etched regions. 8.5 nm Nb2O5 and 49 nm SiO2 thin films were deposited by magnetron sputtering as index-matching layers between an ITO electrode and a glass substrate. In case of 30 nm ITO electrode, a 4.3% improvement in the optical transmittance and a deltaR of less than 1% were achieved, along with a low sheet resistance of 90 omega/square.

  20. Synthesis and electrochemical capacitance of long tungsten oxide nanorod arrays grown vertically on substrate

    SciTech Connect

    Park, Sun Hwa; Kim, Young Heon; Lee, Tae Geol; Shon, Hyun Kyong; Park, Hyun Min; Song, Jae Yong

    2012-11-15

    Highlights: ► Growth of long amorphous tungsten oxide nanorods on a substrate. ► Formation of single-crystalline tungsten oxide nanorods by a heat-treatment. ► High electrochemical pseudocapacitance of 2.8 mF cm{sup −2}. ► Excellent cyclability of psuedocapacitance up to 1000 cycles. -- Abstract: Long tungsten oxide nanorods are vertically grown on Al/W/Ti coated silicon substrates using a two-step anodization process. The first anodization of the Al film forms a mesh-like mask of anodic aluminum oxide, and the second anodization of the W film results in the formation of a buffer layer, a bottom nanorod, and a top nanorod of amorphous tungsten oxide. A pore-widening process prior to the second anodization leads to the enhancement of nanorod length above approximately 500 nm. After a heat-treatment, the tungsten oxide nanorods are crystallized to form a single crystalline structure while the buffer layer forms a polycrystalline structure. The crystalline tungsten oxide nanorods show a cyclic voltammogram retaining the quasi-rectangular shape of an electrochemically reversible faradaic redox reaction, i.e., a typical pseudocapacitive behavior. The maximum electrochemical capacitance per apparent surface area reaches approximately 2.8 mF cm{sup −2} at the voltage scan rate of 20 mV s{sup −1}, and the excellent cyclability of charge–discharge process is maintained up to 1000 cycles.

  1. Reduced graphene oxide hydrogels deposited in nickel foam for supercapacitor applications: Toward high volumetric capacitance

    DOE PAGES

    Pham, Viet Hung; Dickerson, James H.

    2016-02-21

    Graphene hydrogels have been considered as ideal materials for high-performance supercapacitors. However, their low volumetric capacitance significantly limits its real application. In this study, we report an environment-friendly and scalable method to prepare high packing density, electrochemically reduced graphene oxide hydrogels (ERGO) for supercapacitor application by the electrophoretic deposition of graphene oxide onto nickel foam, followed by the electrochemical reduction and hydraulic compression of the deposited materials. The as-prepared ERGO on nickel foam was hydraulic compressed up to 20 tons, resulting in an increase of the packing density of ERGO from 0.0098 to 1.32 g cm–3. Consequently, the volumetric capacitancemore » and volumetric energy density of ERGOs greatly increased from 1.58 F cm–3 and 0.053 Wh cm–3 (as-prepared ERGO) to 176.5 F cm–3 and 6.02 Wh cm–3 (ERGO compressed at 20 tons), respectively. The ERGOs also exhibited long-term electrochemical stability with a capacitance retention in the range of approximately 79–90% after 10 000 cycles. Lastly, we believe that these high packing density ERGOs are promising for real-world energy storage devices for which scalable, cost-effective manufacturing is of significance and for which space constraints are paramount.« less

  2. Study of GaAs-oxide interface by transient capacitance spectroscopy - Discrete energy interface states

    NASA Technical Reports Server (NTRS)

    Kamieniecki, E.; Kazior, T. E.; Lagowski, J.; Gatos, H. C.

    1980-01-01

    Interface states and bulk GaAs energy levels were simultaneously investigated in GaAs MOS structures prepared by anodic oxidation. These two types of energy levels were successfully distinguished by carrying out a comparative analysis of deep level transient capacitance spectra of the MOS structures and MS structures prepared on the same samples of epitaxially grown GaAs. The identification and study of the interface states and bulk levels was also performed by investigating the transient capacitance spectra as a function of the filling pulse magnitude. It was found that in the GaAs-anodic oxide interface there are states present with a discrete energy rather than with a continuous energy distribution. The value of the capture cross section of the interface states was found to be 10 to the 14th to 10 to the 15th/sq cm, which is more accurate than the extremely large values of 10 to the -8th to 10 to the -9th/sq cm reported on the basis of conductance measurements.

  3. Compliment Graphene Oxide Coating on Silk Fiber Surface via Electrostatic Force for Capacitive Humidity Sensor Applications

    PubMed Central

    Han, Kook In; Kim, Seungdu; Lee, In Gyu; Kim, Jong Pil; Kim, Jung-Ha; Hong, Suck Won; Cho, Byung Jin; Hwang, Wan Sik

    2017-01-01

    Cylindrical silk fiber (SF) was coated with Graphene oxide (GO) for capacitive humidity sensor applications. Negatively charged GO in the solution was attracted to the positively charged SF surface via electrostatic force without any help from adhesive intermediates. The magnitude of the positively charged SF surface was controlled through the static electricity charges created on the SF surface. The GO coating ability on the SF improved as the SF’s positive charge increased. The GO-coated SFs at various conditions were characterized using an optical microscope, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and LCR meter. Unlike the intact SF, the GO-coated SF showed clear response-recovery behavior and well-behaved repeatability when it was exposed to 20% relative humidity (RH) and 90% RH alternatively in a capacitive mode. This approach allows humidity sensors to take advantage of GO’s excellent sensing properties and SF’s flexibility, expediting the production of flexible, low power consumption devices at relatively low costs. PMID:28218728

  4. Compliment Graphene Oxide Coating on Silk Fiber Surface via Electrostatic Force for Capacitive Humidity Sensor Applications.

    PubMed

    Han, Kook In; Kim, Seungdu; Lee, In Gyu; Kim, Jong Pil; Kim, Jung-Ha; Hong, Suck Won; Cho, Byung Jin; Hwang, Wan Sik

    2017-02-19

    Cylindrical silk fiber (SF) was coated with Graphene oxide (GO) for capacitive humidity sensor applications. Negatively charged GO in the solution was attracted to the positively charged SF surface via electrostatic force without any help from adhesive intermediates. The magnitude of the positively charged SF surface was controlled through the static electricity charges created on the SF surface. The GO coating ability on the SF improved as the SF's positive charge increased. The GO-coated SFs at various conditions were characterized using an optical microscope, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and LCR meter. Unlike the intact SF, the GO-coated SF showed clear response-recovery behavior and well-behaved repeatability when it was exposed to 20% relative humidity (RH) and 90% RH alternatively in a capacitive mode. This approach allows humidity sensors to take advantage of GO's excellent sensing properties and SF's flexibility, expediting the production of flexible, low power consumption devices at relatively low costs.

  5. Electrochemical DNA biosensors based on thin gold films sputtered on capacitive nanoporous niobium oxide.

    PubMed

    Rho, Sangchul; Jahng, Deokjin; Lim, Jae Hoon; Choi, Jinsub; Chang, Jeong Ho; Lee, Sang Cheon; Kim, Kyung Ja

    2008-01-18

    Electrochemical DNA biosensors based on a thin gold film sputtered on anodic porous niobium oxide (Au@Nb(2)O(5)) are studied in detail here. We found that the novel DNA biosensor based on Au@Nb(2)O(5) is superior to those based on the bulk gold electrode or niobium oxide electrode. For example, the novel method does not require any time-consuming cleaning step in order to obtain reproducible results. The adhesion of gold films on the substrate is very stable during electrochemical biosensing, when the thin gold films are deposited on anodically prepared nanoporous niobium oxide. In particular, the novel biosensor shows enhanced biosensing performance with a 2.4 times higher resolution and a three times higher sensitivity. The signal enhancement is in part attributed to capacitive interface between gold films and nanoporous niobium oxide, where charges are accumulated during the anodic and cathodic scanning, and is in part ascribed to the structural stability of DNA immobilized at the sputtered gold films. The method allows for the detection of single-base mismatch DNA as well as for the discrimination of mismatch positions.

  6. Facile preparation of polypyrrole/graphene oxide nanocomposites with large areal capacitance using electrochemical codeposition for supercapacitors

    NASA Astrophysics Data System (ADS)

    Zhou, Haihan; Han, Gaoyi; Xiao, Yaoming; Chang, Yunzhen; Zhai, Hua-Jin

    2014-10-01

    A simple and low-cost electrochemical codeposition method has been introduced to fabricate polypyrrole/graphene oxide (PPy/GO) nanocomposites and the areal capacitance of conducting polymer/GO composites is reported for the first time. Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) are implemented to determine the PPy/GO nanocomposites are successfully prepared and the interaction between PPy and GO. The as-prepared PPy/GO nanocomposites show the curly sheet-like morphology, superior capacitive behaviors and cyclic stability. Furthermore, the varying deposition time is implemented to investigate the impact of the loading amount on electrochemical behavior of the composites, and a high areal capacitance of 152 mF cm-2 is achieved at 10 mV s-1 CV scan. However, the thicker films caused by the long deposition time would result in larger diffusion resistance of electrolyte ions, consequently exhibit the relatively lower capacitance value at the high current density. The GCD tests indicate moderate deposition time is more suitable for the fast charge/discharge. Considering the very simple and effective synthetic process, the PPy/GO nanocomposites with relatively high areal capacitance are competitive candidate for supercapacitor application, and its capacitive performances can be easily tuned by varying the deposition time.

  7. Pseudo capacitive performance of copper oxide thin films grown by RF sputtering

    SciTech Connect

    Reddy, B. Purusottam; Ganesh, K. Sivajee; Hussain, O. M.

    2015-06-24

    Thin films of Copper Oxide were prepared by radio frequency magnetron sputtering on steel substrates maintained at 250°C under different RF powers ranging from 150W to 250W by keeping the sputtering pressure at 5.7×10{sup −3} mbar and O{sub 2}:Ar ratio of 1:7. The influence of RF power on the pseudo capacitive performance of thin films was studied. The X-ray diffraction studies and Raman studies indicates that all the thin films exhibits CuO phase. The electrochemical studies was done by using three electrode configuration with platinum as reference electrode. From the cyclic voltammetry studies a high rate pseudocapacitance of 227 mFcm{sup −2} at 0.5 mVs{sup −1} and 77% of capacity retention after 1000 cycles was obtained for the CuO thin films prepared at an RF power of 220W.

  8. Enhancing capacitance behaviour of CoOOH nanostructures using transition metal dopants by ambient oxidation

    PubMed Central

    Chen, Yanhui; Zhou, Junfeng; Maguire, Pierce; O’Connell, Robert; Schmitt, Wolfgang; Li, Yonghe; Yan, Zhengguang; Zhang, Yuefei; Zhang, Hongzhou

    2016-01-01

    Cobalt hydrate and doped binary Co0.9M0.1OOH (M = Ni, Mn, Fe) nanorings of 100–300 nm were fabricated in solution through a facile ambient oxidation method. A transformation from Co0.9Ni0.1(OH)2 nanodiscs to hollow Co0.9Ni0.1OOH nanorings was observed with prolonged reaction time. Core-shell nanodiscs have elemental segregation with a Co(OH)2 core and Ni(OH)2 shell. Co0.9Ni0.1OOH nanorings displayed a higher electrochemical capacitance than Mn and Fe doped nanorings materials or materials with disc-like geometries. PMID:26853105

  9. Inhibiting Wet Oxidation of Ammonia

    NASA Technical Reports Server (NTRS)

    Onisko, D. B. L.

    1985-01-01

    Simple modification of wet-oxidation process for treating organicwaste reduces loss of fixed nitrogen, potentially valuable byproduct of process. Addition of sufficient sulfuric acid to maintain reaction pH below 3 greatly reduces oxidation of ammonia to free nitrogen. No equipment modification required.

  10. Nickel inhibits mitochondrial fatty acid oxidation.

    PubMed

    Uppala, Radha; McKinney, Richard W; Brant, Kelly A; Fabisiak, James P; Goetzman, Eric S

    2015-08-07

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation-the pathway by which fatty acids are catabolized for energy-in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with l-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 h), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis.

  11. Equivalent distributed capacitance model of oxide traps on frequency dispersion of C-V curve for MOS capacitors

    NASA Astrophysics Data System (ADS)

    Lu, Han-Han; Xu, Jing-Ping; Liu, Lu; Lai, Pui-To; Tang, Wing-Man

    2016-11-01

    An equivalent distributed capacitance model is established by considering only the gate oxide-trap capacitance to explain the frequency dispersion in the C-V curve of MOS capacitors measured for a frequency range from 1 kHz to 1 MHz. The proposed model is based on the Fermi-Dirac statistics and the charging/discharging effects of the oxide traps induced by a small ac signal. The validity of the proposed model is confirmed by the good agreement between the simulated results and experimental data. Simulations indicate that the capacitance dispersion of an MOS capacitor under accumulation and near flatband is mainly caused by traps adjacent to the oxide/semiconductor interface, with negligible effects from the traps far from the interface, and the relevant distance from the interface at which the traps can still contribute to the gate capacitance is also discussed. In addition, by excluding the negligible effect of oxide-trap conductance, the model avoids the use of imaginary numbers and complex calculations, and thus is simple and intuitive. Project supported by the National Natural Science Foundation of China (Grant Nos. 61176100 and 61274112), the University Development Fund of the University of Hong Kong, China (Grant No. 00600009), and the Hong Kong Polytechnic University, China (Grant No. 1-ZVB1).

  12. Effect of oxidation of carbon material on suspension electrodes for flow electrode capacitive deionization.

    PubMed

    Hatzell, Kelsey B; Hatzell, Marta C; Cook, Kevin M; Boota, Muhammad; Housel, Gabrielle M; McBride, Alexander; Kumbur, E Caglan; Gogotsi, Yury

    2015-03-03

    Flow electrode deionization (FCDI) is an emerging area for continuous and scalable deionization, but the electrochemical and flow properties of the flow electrode need to be improved to minimize energy consumption. Chemical oxidation of granular activated carbon (AC) was examined here to study the role of surface heteroatoms on rheology and electrochemical performance of a flow electrode (carbon slurry) for deionization processes. Moreover, it was demonstrated that higher mass densities could be used without increasing energy for pumping when using oxidized active material. High mass-loaded flow electrodes (28% carbon content) based on oxidized AC displayed similar viscosities (∼21 Pa s) to lower mass-loaded flow electrodes (20% carbon content) based on nonoxidized AC. The 40% increased mass loading (from 20% to 28%) resulted in a 25% increase in flow electrode gravimetric capacitance (from 65 to 83 F g(-1)) without sacrificing flowability (viscosity). The electrical energy required to remove ∼18% of the ions (desalt) from of the feed solution was observed to be significantly dependent on the mass loading and decreased (∼60%) from 92 ± 7 to 28 ± 2.7 J with increased mass densities from 5 to 23 wt %. It is shown that the surface chemistry of the active material in a flow electrode effects the electrical and pumping energy requirements of a FCDI system.

  13. Effect of oxidation of carbon material on suspension electrodes for flow electrode capacitive deionization

    SciTech Connect

    Hatzell, Kelsey B.; Hatzell, Marta C.; Cook, Kevin M.; Boota, Muhammad; Housel, Gabrielle M.; Mcbride, Alexander; Kumbur, E. Caglan; Gogotsi, Yury

    2015-01-29

    Flow electrode deionization (FCDI) is an emerging area for continuous and scalable deionization, but the electrochemical and flow properties of the flow electrode need to be improved to minimize energy consumption. We examine chemical oxidation of granular activated carbon (AC) here to study the role of surface heteroatoms on rheology and electrochemical performance of a flow electrode (carbon slurry) for deionization processes. Moreover, it was demonstrated that higher mass densities could be used without increasing energy for pumping when using oxidized active material. High mass-loaded flow electrodes (28% carbon content) based on oxidized AC displayed similar viscosities (~21 Pa s) to lower mass-loaded flow electrodes (20% carbon content) based on nonoxidized AC. The 40% increased mass loading (from 20% to 28%) resulted in a 25% increase in flow electrode gravimetric capacitance (from 65 to 83 F g–1) without sacrificing flowability (viscosity). The electrical energy required to remove ~18% of the ions (desalt) from of the feed solution was observed to be significantly dependent on the mass loading and decreased (~60%) from 92 ± 7 to 28 ± 2.7 J with increased mass densities from 5 to 23 wt %. Finally, it is shown that the surface chemistry of the active material in a flow electrode effects the electrical and pumping energy requirements of a FCDI system.

  14. Effect of oxidation of carbon material on suspension electrodes for flow electrode capacitive deionization

    DOE PAGES

    Hatzell, Kelsey B.; Hatzell, Marta C.; Cook, Kevin M.; ...

    2015-01-29

    Flow electrode deionization (FCDI) is an emerging area for continuous and scalable deionization, but the electrochemical and flow properties of the flow electrode need to be improved to minimize energy consumption. We examine chemical oxidation of granular activated carbon (AC) here to study the role of surface heteroatoms on rheology and electrochemical performance of a flow electrode (carbon slurry) for deionization processes. Moreover, it was demonstrated that higher mass densities could be used without increasing energy for pumping when using oxidized active material. High mass-loaded flow electrodes (28% carbon content) based on oxidized AC displayed similar viscosities (~21 Pa s)more » to lower mass-loaded flow electrodes (20% carbon content) based on nonoxidized AC. The 40% increased mass loading (from 20% to 28%) resulted in a 25% increase in flow electrode gravimetric capacitance (from 65 to 83 F g–1) without sacrificing flowability (viscosity). The electrical energy required to remove ~18% of the ions (desalt) from of the feed solution was observed to be significantly dependent on the mass loading and decreased (~60%) from 92 ± 7 to 28 ± 2.7 J with increased mass densities from 5 to 23 wt %. Finally, it is shown that the surface chemistry of the active material in a flow electrode effects the electrical and pumping energy requirements of a FCDI system.« less

  15. Nickel Inhibits Mitochondrial Fatty Acid Oxidation

    PubMed Central

    Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

    2015-01-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  16. Vanadium Oxide Electrochemical Capacitors: An Investigation into Aqueous Capacitive Degradation, Alternate Electrolyte-Solvent Systems, Whole Cell Performance and Graphene Oxide Composite Electrodes

    NASA Astrophysics Data System (ADS)

    Engstrom, Allison Michelle

    Vanadium oxide has emerged as a potential electrochemical capacitor material due to its attractive pseudocapacitive performance; however, it is known to suffer from capacitive degradation upon sustained cycling. In this work, the electrochemical cycling behavior of anodically electrodeposited vanadium oxide films with various surface treatments in aqueous solutions is investigated at different pH. Quantitative compositional analysis and morphological studies provide additional insight into the mechanism responsible for capacitive degradation. Furthermore, the capacitance and impedance behavior of vanadium oxide electrochemical capacitor electrodes is compared for both aqueous and nonaqueous electrolyte-solvent systems. Alkali metal chloride and bromide electrolytes were studied in aqueous systems, and nonaqueous systems containing alkali metal bromides were studied in polar aprotic propylene carbonate (PC) or dimethyl sulfoxide (DMSO) solvents. The preferred aqueous and nonaqueous systems identified in the half-cell studies were utilized in symmetric vanadium oxide whole-cells. An aqueous system utilizing a 3.0 M NaCl electrolyte at pH 3.0 exhibited an excellent 96% capacitance retention over 3000 cycles at 10 mV s-1. An equivalent system tested at 500 mV s-1 displayed an increase in capacitance over the first several thousands of cycles, and eventually stabilized over 50,000 cycles. Electrodes cycled in nonaqueous 1.0 M LiBr in PC exhibited mostly non-capacitive charge-storage, and electrodes cycled in LiBr-DMSO exhibited a gradual capacitive decay over 10,000 cycles at 500 mV s-1. Morphological and compositional analyses, as well as electrochemical impedance modeling, provide additional insight into the cause of the cycing behavior. Lastly, reduced graphene oxide and vanadium oxide nanowire composites have been successfully synthesized using electrophoretic deposition for electrochemical capacitor electrodes. The composite material was found to perform with a

  17. Rescaling of metal oxide nanocrystals for energy storage having high capacitance and energy density with robust cycle life.

    PubMed

    Jeong, Hyung Mo; Choi, Kyung Min; Cheng, Tao; Lee, Dong Ki; Zhou, Renjia; Ock, Il Woo; Milliron, Delia J; Goddard, William A; Kang, Jeung Ku

    2015-06-30

    Nanocrystals are promising structures, but they are too large for achieving maximum energy storage performance. We show that rescaling 3-nm particles through lithiation followed by delithiation leads to high-performance energy storage by realizing high capacitance close to the theoretical capacitance available via ion-to-atom redox reactions. Reactive force-field (ReaxFF) molecular dynamics simulations support the conclusion that Li atoms react with nickel oxide nanocrystals (NiO-n) to form lithiated core-shell structures (Ni:Li2O), whereas subsequent delithiation causes Ni:Li2O to form atomic clusters of NiO-a. This is consistent with in situ X-ray photoelectron and optical spectroscopy results showing that Ni(2+) of the nanocrystal changes during lithiation-delithiation through Ni(0) and back to Ni(2+). These processes are also demonstrated to provide a generic route to rescale another metal oxide. Furthermore, assembling NiO-a into the positive electrode of an asymmetric device enables extraction of full capacitance for a counter negative electrode, giving high energy density in addition to robust capacitance retention over 100,000 cycles.

  18. Rescaling of metal oxide nanocrystals for energy storage having high capacitance and energy density with robust cycle life

    PubMed Central

    Jeong, Hyung Mo; Choi, Kyung Min; Cheng, Tao; Lee, Dong Ki; Zhou, Renjia; Ock, Il Woo; Milliron, Delia J.; Goddard, William A.; Kang, Jeung Ku

    2015-01-01

    Nanocrystals are promising structures, but they are too large for achieving maximum energy storage performance. We show that rescaling 3-nm particles through lithiation followed by delithiation leads to high-performance energy storage by realizing high capacitance close to the theoretical capacitance available via ion-to-atom redox reactions. Reactive force-field (ReaxFF) molecular dynamics simulations support the conclusion that Li atoms react with nickel oxide nanocrystals (NiO-n) to form lithiated core–shell structures (Ni:Li2O), whereas subsequent delithiation causes Ni:Li2O to form atomic clusters of NiO-a. This is consistent with in situ X-ray photoelectron and optical spectroscopy results showing that Ni2+ of the nanocrystal changes during lithiation–delithiation through Ni0 and back to Ni2+. These processes are also demonstrated to provide a generic route to rescale another metal oxide. Furthermore, assembling NiO-a into the positive electrode of an asymmetric device enables extraction of full capacitance for a counter negative electrode, giving high energy density in addition to robust capacitance retention over 100,000 cycles. PMID:26080421

  19. Computer Simulation and Measurement of Capacitance-Voltage Characteristics in Quantum Wire Devices of Trench-Oxide MOS Structure

    NASA Astrophysics Data System (ADS)

    Tsukui, Tetsuya; Oda, Shunri

    1995-02-01

    We have proposed the trench-oxide metal-oxide-semiconductor (MOS) structure as a novel quantum wire device. In this paper we present results of computer simulation based on a self-consistent system and calculated quantized electron distribution and capacitance-voltage (C-V) characteristics. We have also fabricated the quantum wire MOS structure using electron beam lithography and electron cyclotron resonance reactive ion etching method and carried out measurements of C-V characteristics at 0.55 K. Possible evidence of one-dimensional quantum effect is obtained for the first time from C-V measurements using the 28 nm-wide trench-oxide structure.

  20. Fabrication and Evaluation of a Graphene Oxide-Based Capacitive Humidity Sensor.

    PubMed

    Feng, Jinfeng; Kang, Xiaoxu; Zuo, Qingyun; Yuan, Chao; Wang, Weijun; Zhao, Yuhang; Zhu, Limin; Lu, Hanwei; Chen, Juying

    2016-03-01

    In this study, a CMOS compatible capacitive humidity sensor structure was designed and fabricated on a 200 mm CMOS BEOL Line. A top Al interconnect layer was used as an electrode with a comb/serpent structure, and graphene oxide (GO) was used as sensing material. XRD analysis was done which shows that GO sensing material has a strong and sharp (002) peak at about 10.278°, whereas graphite has (002) peak at about 26°. Device level CV and IV curves were measured in mini-environments at different relative humidity (RH) level, and saturated salt solutions were used to build these mini-environments. To evaluate the potential value of GO material in humidity sensor applications, a prototype humidity sensor was designed and fabricated by integrating the sensor with a dedicated readout ASIC and display/calibration module. Measurements in different mini-environments show that the GO-based humidity sensor has higher sensitivity, faster recovery time and good linearity performance. Compared with a standard humidity sensor, the measured RH data of our prototype humidity sensor can match well that of the standard product.

  1. Inhibiting Metal Oxide Atomic Layer Deposition: Beyond Zinc Oxide.

    PubMed

    Sampson, Matthew D; Emery, Jonathan D; Pellin, Michael J; Martinson, Alex B F

    2017-04-05

    Atomic layer deposition (ALD) of several metal oxides is selectivity inhibited on alkanethiol self-assembled monolayers (SAMs) on Au, and the eventual nucleation mechanism is investigated. The inhibition ability of the SAM is significantly improved by the in situ H2-plasma pretreatment of the Au substrate prior to the gas-phase deposition of a long-chain alkanethiol, 1-dodecanethiol (DDT). This more rigorous surface preparation inhibits even aggressive oxide ALD precursors, including trimethylaluminum and water, for at least 20 cycles. We study the effect that the ALD precursor purge times, growth temperature, alkanethiol chain length, alkanethiol deposition time, and plasma treatment time have on Al2O3 ALD inhibition. This is the first example of Al2O3 ALD inhibition from a vapor-deposited SAM. The inhibitions of Al2O3, ZnO, and MnO ALD processes are compared, revealing the versatility of this selective surface treatment. Atomic force microscopy and grazing-incidence X-ray fluorescence further reveal insight into the mechanism by which the well-defined surface chemistry of ALD may eventually be circumvented to allow metal oxide nucleation and growth on SAM-modified surfaces.

  2. A mixed solution-processed gate dielectric for zinc-tin oxide thin-film transistor and its MIS capacitance

    NASA Astrophysics Data System (ADS)

    Kim, Hunho; Kwack, Young-Jin; Yun, Eui-Jung; Choi, Woon-Seop

    2016-09-01

    Solution-processed gate dielectrics were fabricated with the combined ZrO2 and Al2O3 (ZAO) in the form of mixed and stacked types for oxide thin film transistors (TFTs). ZAO thin films prepared with double coatings for solid gate dielectrics were characterized by analytical tools. For the first time, the capacitance of the oxide semiconductor was extracted from the capacitance-voltage properties of the zinc-tin oxide (ZTO) TFTs with the combined ZAO dielectrics by using the proposed metal-insulator-semiconductor (MIS) structure model. The capacitance evolution of the semiconductor from the TFT model structure described well the threshold voltage shift observed in the ZTO TFT with the ZAO (1:2) gate dielectric. The electrical properties of the ZTO TFT with a ZAO (1:2) gate dielectric showed low voltage driving with a field effect mobility of 37.01 cm2/Vs, a threshold voltage of 2.00 V, an on-to-off current ratio of 1.46 × 105, and a subthreshold slope of 0.10 V/dec.

  3. A mixed solution-processed gate dielectric for zinc-tin oxide thin-film transistor and its MIS capacitance

    PubMed Central

    Kim, Hunho; Kwack, Young-Jin; Yun, Eui-Jung; Choi, Woon-Seop

    2016-01-01

    Solution-processed gate dielectrics were fabricated with the combined ZrO2 and Al2O3 (ZAO) in the form of mixed and stacked types for oxide thin film transistors (TFTs). ZAO thin films prepared with double coatings for solid gate dielectrics were characterized by analytical tools. For the first time, the capacitance of the oxide semiconductor was extracted from the capacitance-voltage properties of the zinc-tin oxide (ZTO) TFTs with the combined ZAO dielectrics by using the proposed metal-insulator-semiconductor (MIS) structure model. The capacitance evolution of the semiconductor from the TFT model structure described well the threshold voltage shift observed in the ZTO TFT with the ZAO (1:2) gate dielectric. The electrical properties of the ZTO TFT with a ZAO (1:2) gate dielectric showed low voltage driving with a field effect mobility of 37.01 cm2/Vs, a threshold voltage of 2.00 V, an on-to-off current ratio of 1.46 × 105, and a subthreshold slope of 0.10 V/dec. PMID:27641430

  4. Caffeine inhibits InsP3 responses and capacitative calcium entry in canine pulmonary arterial smooth muscle cells.

    PubMed

    Hume, Joseph R; McAllister, Claire E; Wilson, Sean M

    2009-01-01

    Caffeine is a well described and characterized ryanodine receptor (RyR) activator. Previous evidence from independent research studies also indicate caffeine inhibits InsP3 receptor functionality, which is important to activation of capacitative Ca2+ entry (CCE) in some cell types. In addition, RyR activation elicits excitatory-coupled Ca2+ entry (ECCE) in skeletal muscle myotubes. Recent studies by our group show that canine pulmonary arterial smooth muscle cells (PASMCs) have functional InsP3 receptors as well as RyRs, and that CCE is dependent on InsP3 receptor activity. The potential for caffeine to activate ECCE as well as inhibit InsP3 receptor function and CCE was examined using fura-2 fluorescent imaging in canine PASMCs. The data show caffeine causes transient as well as sustained cytosolic Ca2+ increases, though this is not due to CCE or ECCE activity as evidenced by a lack of an increase in Mn2+ quench of fura-2. The experiments also show caffeine reversibly inhibits 5-HT elicited-InsP3 mediated Ca2+ responses with an IC50 of 6.87x10(-4) M and 10 mM caffeine fully inhibits CCE. These studies provide the first evidence that caffeine is an inhibitor of InsP3 generated Ca2+ signals and CCE in PASMCs.

  5. Detection of IFN-γ for latent tuberculosis diagnosis using an anodized aluminum oxide-based capacitive sensor.

    PubMed

    Kim, Joo Hyoung; Chang, Young Wook; Bok, Eun; Kim, Hyun-Jeong; Lee, Hyejon; Cho, Sang-Nae; Shin, Jeon-Soo; Yoo, Kyung-Hwa

    2014-01-15

    We describe a rapid, sensitive, and label-free method to detect interferon-gamma (IFN-γ), a biomarker of latent tuberculosis infection (LTBI). IFN-γ is detected by measuring the capacitance change caused by its binding to an anti-IFN-γ antibody. The antibody is immobilized on the surface of an anodized aluminum oxide (AAO)-based capacitive sensor. With this technique, IFN-γ can be detected in the range of ~0.1 pg/ml to ~10 ng/ml, with a detection limit of 0.2 pg/ml. We have also measured the concentration of IFN-γ in clinical samples using the AAO-based capacitive sensor and compared this concentration with the results of the commercial QuantiFERON-TB Gold (QFT-G) ELISA kit to determine whether the two sets of data are consistent. Comparable results were obtained with the two measurement strategies, demonstrating the applicability of the AAO-based capacitive sensor to the diagnosis of LTBI.

  6. Measurement of n-type Dry Thermally Oxidized 6H-SiC Metal-oxide Semiconductor Diodes by Quasistatic and High-Frequency Capacitance Versus Voltage and Capacitance Transient Techniques

    NASA Technical Reports Server (NTRS)

    Neudeck, P.; Kang, S.; Petit, J.; Tabib-Azar, M.

    1994-01-01

    Dry-oxidized n-type 6H-SiC metal-oxide-semiconductor capacitors are investigated using quasistatic capacitance versus voltage (C-V), high-frequency C-V, and pulsed high-frequency capacitance transient (C-t) analysis over the temperature range from 297 to 573 K. The quasistatic C - V characteristics presented are the first reported for 6H-SiC MOS capacitors, and exhibit startling nonidealities due to nonequilibrium conditions that arise from the fact that the recombination/generation process in 6H-SiC is extraordinarily slow even at the highest measurement temperature employed. The high-frequency dark C-V characteristics all showed deep depletion with no observable hysteresis. The recovery of the high-frequency capacitance from deep depletion to inversion was used to characterize the minority-carrier generation process as a function of temperature. Zerbst analysis conducted on the resulting C-t transients, which were longer than 1000 s at 573 K, showed a generation lifetime thermal activation energy of 0.49 eV.

  7. Nitric oxide scavengers differentially inhibit ammonia oxidation in ammonia-oxidizing archaea and bacteria.

    PubMed

    Sauder, Laura A; Ross, Ashley A; Neufeld, Josh D

    2016-04-01

    Differential inhibitors are important for measuring the relative contributions of microbial groups, such as ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA), to biogeochemical processes in environmental samples. In particular, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) represents a nitric oxide scavenger used for the specific inhibition of AOA, implicating nitric oxide as an intermediate of thaumarchaeotal ammonia oxidation. This study investigated four alternative nitric oxide scavengers for their ability to differentially inhibit AOA and AOB in comparison to PTIO. Caffeic acid, curcumin, methylene blue hydrate and trolox were tested onNitrosopumilus maritimus, two unpublished AOA representatives (AOA-6f and AOA-G6) as well as the AOB representative Nitrosomonas europaea All four scavengers inhibited ammonia oxidation by AOA at lower concentrations than for AOB. In particular, differential inhibition of AOA and AOB by caffeic acid (100 μM) and methylene blue hydrate (3 μM) was comparable to carboxy-PTIO (100 μM) in pure and enrichment culture incubations. However, when added to aquarium sponge biofilm microcosms, both scavengers were unable to inhibit ammonia oxidation consistently, likely due to degradation of the inhibitors themselves. This study provides evidence that a variety of nitric oxide scavengers result in differential inhibition of ammonia oxidation in AOA and AOB, and provides support to the proposed role of nitric oxide as a key intermediate in the thaumarchaeotal ammonia oxidation pathway.

  8. Inhibition of tyrosine phosphorylation of sperm flagellar proteins, outer dense fiber protein-2 and tektin-2, is associated with impaired motility during capacitation of hamster spermatozoa.

    PubMed

    Mariappa, Daniel; Aladakatti, Ravindranath H; Dasari, Santosh K; Sreekumar, Arun; Wolkowicz, Michael; van der Hoorn, Frans; Seshagiri, Polani B

    2010-02-01

    In mammals, acquisition of fertilization competence of spermatozoa is dependent on the phenomenon of sperm capacitation. One of the critical molecular events of sperm capacitation is protein tyrosine phosphorylation. In a previous study, we demonstrated that a specific epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, tyrphostin-A47, inhibited hamster sperm capacitation, accompanied by a reduced sperm protein tyrosine phosphorylation. Interestingly, a high percentage of tyrphostin-A47-treated spermatozoa exhibited circular motility, which was associated with a distinct hypo-tyrosine phosphorylation of flagellar proteins, predominantly of Mr 45,000-60,000. In this study, we provide evidence on the localization of capacitation-associated tyrosine-phosphorylated proteins to the nonmembranous, structural components of the sperm flagellum. Consistent with this, we show their ultrastructural localization in the outer dense fiber, axoneme, and fibrous sheath of spermatozoa. Among hypo-tyrosine phosphorylated major proteins of tyrphostin-A47-treated spermatozoa, we identified the 45 kDa protein as outer dense fiber protein-2 and the 51 kDa protein as tektin-2, components of the sperm outer dense fiber and axoneme, respectively. This study shows functional association of hypo-tyrosine-phosphorylation status of outer dense fiber protein-2 and tektin-2 with impaired flagellar bending of spermatozoa, following inhibition of EGFR-tyrosine kinase, thereby showing the critical importance of flagellar protein tyrosine phosphorylation during capacitation and hyperactivation of hamster spermatozoa.

  9. Inhibition of Oxidation in Nuclear Graphite

    SciTech Connect

    Phil Winston; James W. Sterbentz; William E. Windes

    2013-10-01

    Graphite is a fundamental material of high temperature gas cooled nuclear reactors, providing both structure and neutron moderation. Its high thermal conductivity, chemical inertness, thermal heat capacity, and high thermal structural stability under normal and off normal conditions contribute to the inherent safety of these reactor designs. One of the primary safety issues for a high temperature graphite reactor core is the possibility of rapid oxidation of the carbon structure during an off normal design basis event where an oxidizing atmosphere (air ingress) can be introduced to the hot core. Although the current Generation IV high temperature reactor designs attempt to mitigate any damage caused by a postualed air ingress event, the use of graphite components that inhibit oxidation is a logical step to increase the safety of these reactors. Recent experimental studies of graphite containing between 5.5 and 7 wt% boron carbide (B4C) indicate that oxidation is dramatically reduced even at prolonged exposures at temperatures up to 900°C. The proposed addition of B4C to graphite components in the nuclear core would necessarily be enriched in B-11 isotope in order to minimize B-10 neutron absorption and graphite swelling. The enriched boron can be added to the graphite during billet fabrication. Experimental oxidation rate results and potential applications for borated graphite in nuclear reactor components will be discussed.

  10. Influence of interface traps inside the conduction band on the capacitance-voltage characteristics of InGaAs metal-oxide-semiconductor capacitors

    NASA Astrophysics Data System (ADS)

    Taoka, Noriyuki; Yokoyama, Masafumi; Kim, Sang Hyeon; Suzuki, Rena; Iida, Ryo; Takenaka, Mitsuru; Takagi, Shinichi

    2016-11-01

    We investigated the influences of the AC response with interface/bulk-oxide traps near the conduction band (CB) and a low effective density of states (DOS) on the accumulation capacitance C acc of an n-type InGaAs metal-oxide-semiconductor (MOS) capacitor. We found that the capacitance associated with the interface traps inside the CB significantly increases C acc compared to the C acc value constrained by a low DOS. These results indicate that accurate characterization inside the CB and considering the capacitance due to the interface traps inside the CB in the MOS capacitance-voltage curves are indispensable for accurate characterization of InGaAs MOS interface properties.

  11. Coexistence of high performance resistance and capacitance memory based on multilayered metal-oxide structures

    PubMed Central

    Yan, Z. B.; Liu, J. -M.

    2013-01-01

    The Au/DyMnO3/Nb:SrTiO3/Au stack was demonstrated to be not only a high performance memristor but also a good memcapacitor. The switching time is below 10 ns, the retention is longer than 105 s, and the change ratio of resistance (or capacitance) is larger than 100 over the 108 switching cycles. Moreover, this stack has a broad range of intermediate states that are tunable by the operating voltages. It is indicated that the memory effects originate from the Nb:SrTiO3/Au junction where the barrier profile is electrically modulated. The serial connected Au/DyMnO3/Nb:SrTiO3 stack behaves as a high nonlinear resistor paralleling with a capacitor, which raises the capacitance change ratio and enhances the memory stability of the device. PMID:23963467

  12. Coexistence of high performance resistance and capacitance memory based on multilayered metal-oxide structures.

    PubMed

    Yan, Z B; Liu, J-M

    2013-01-01

    The Au/DyMnO₃/Nb:SrTiO₃/Au stack was demonstrated to be not only a high performance memristor but also a good memcapacitor. The switching time is below 10 ns, the retention is longer than 10(5) s, and the change ratio of resistance (or capacitance) is larger than 100 over the 10(8) switching cycles. Moreover, this stack has a broad range of intermediate states that are tunable by the operating voltages. It is indicated that the memory effects originate from the Nb:SrTiO₃/Au junction where the barrier profile is electrically modulated. The serial connected Au/DyMnO₃/Nb:SrTiO₃ stack behaves as a high nonlinear resistor paralleling with a capacitor, which raises the capacitance change ratio and enhances the memory stability of the device.

  13. The influence of electron energy quantization in a space-charge region on the accumulation capacitance of InAs metal-oxide-semiconductor capacitors

    SciTech Connect

    Kovchavtsev, A. P. Tsarenko, A. V.; Guzev, A. A.; Polovinkin, V. G.; Nastovjak, A. E.; Valisheva, N. A.; Aksenov, M. S.

    2015-09-28

    The influence of electron energy quantization in a space-charge region on the accumulation capacitance of the InAs-based metal-oxide-semiconductor capacitors (MOSCAPs) has been investigated by modeling and comparison with the experimental data from Au/anodic layer(4-20 nm)/n-InAs(111)A MOSCAPs. The accumulation capacitance for MOSCAPs has been calculated by the solution of Poisson equation with different assumptions and the self-consistent solution of Schrödinger and Poisson equations with quantization taken into account. It was shown that the quantization during the MOSCAPs accumulation capacitance calculations should be taken into consideration for the correct interface states density determination by Terman method and the evaluation of gate dielectric thickness from capacitance-voltage measurements.

  14. Method for inhibiting oxidation of metal sulfide-containing material

    DOEpatents

    Elsetinow, Alicia; Borda, Michael J.; Schoonen, Martin A.; Strongin, Daniel R.

    2006-12-26

    The present invention provides means for inhibiting the oxidation of a metal sulfide-containing material, such as ore mine waste rock or metal sulfide taiulings, by coating the metal sulfide-containing material with an oxidation-inhibiting two-tail lipid coating (12) thereon, thereby inhibiting oxidation of the metal sulfide-containing material in acid mine drainage conditions. The lipids may be selected from phospholipids, sphingolipids, glycolipids and combinations thereof.

  15. Oxidation inhibits iron-induced blood coagulation.

    PubMed

    Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw

    2013-01-01

    Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and neurological disorders, fibrin clots are very different forming dense matted deposits (DMD) that are not effectively removed and thus create a condition known as thrombosis. We have recently shown that trivalent iron (ferric ions) generates hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in the form of DMDs. A characteristic feature of DMDs is their remarkable and permanent resistance to the enzymatic degradation. Therefore, in order to prevent thrombotic incidences in the degenerative diseases it is essential to inhibit the iron-induced generation of hydroxyl radicals. This can be achieved by the pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown in this paper by the treatment with oxidizing agents such as hydrogen peroxide, methylene blue, and sodium selenite. Although the actual mechanism of this phenomenon is not yet known, it is possible that hydroxyl radicals are neutralized by their conversion to the molecular oxygen and water, thus inhibiting the formation of dense matted fibrin deposits in human blood.

  16. Fabrication of a metal-oxide-semiconductor-type capacitive microtip array using SiO2 or HfO2 gate insulators

    NASA Astrophysics Data System (ADS)

    Kim, Kyung-Min; Choi, Byung Joon; Kim, Seong Keun; Hwang, Cheol Seong

    2004-11-01

    Capacitive tip arrays having a metal-insulator-semiconductor capacitor structure were fabricated using thermally oxidized SiO2 or atomic-layer-deposited HfO2 gate dielectric films for their application to scanning-probe-array-type memory devices. The SiO2 film showed a nonuniform thickness distribution over the flat and tip areas of the arrays owing to the different oxidation speeds of the flat and tip Si surfaces. This resulted in a smaller sensing margin of the device. However, the high-dielectric HfO2 film showed not only a higher capacitance value but also a more uniform growth behavior over the whole area, which would result in a better device performance. The capacitance-voltage characteristics of both devices coincide well with the simulation results based on conventional metal-insulator-semiconductor theories.

  17. Nitric oxide synthases: structure, function and inhibition.

    PubMed Central

    Alderton, W K; Cooper, C E; Knowles, R G

    2001-01-01

    This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in our understanding of this enzyme family. There is now information on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure. The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, L-arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role of the biopterin cofactor is now becoming clearer, with emerging data implicating one-electron redox cycling as well as the multiple allosteric effects on enzyme activity. Regulation of the NOSs has been described at all levels from gene transcription to covalent modification and allosteric regulation of the enzyme itself. A wide range of NOS inhibitors have been discussed, interacting with the enzyme in diverse ways in terms of site and mechanism of inhibition, time-dependence and selectivity for individual isoforms, although there are many pitfalls and misunderstandings of these aspects. Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated. PMID:11463332

  18. Hyaluronic acid as capacitation inductor: metabolic changes and membrane-associated adenylate cyclase regulation.

    PubMed

    Fernández, S; Córdoba, M

    2014-12-01

    The aim of this research was to study the effect of hyaluronic acid on bovine cryopreserved spermatozoa compared with heparin as regards the variation of capacitation induction, cellular oxidative metabolism and intracellular signal induced by membrane-associated adenylate cyclase to propose hyaluronic acid as a capacitation inductor. Heparin or hyaluronic acid and lysophosphatidylcholine were used to induce sperm capacitation and acrosome reaction, respectively. 2',5'-dideoxyadenosine was used as a membrane-associated adenylate cyclase inhibitor. The highest percentages of capacitated spermatozoa and live spermatozoa with acrosome integrity were obtained by incubating sperm for 60 min using 1000 μg/ml hyaluronic acid. In these conditions, capacitation induced by hyaluronic acid was lower compared with heparin; nonetheless both glycosaminoglycans promote intracellular changes that allow true acrosome reaction in vitro induced by lysophosphatidylcholine in bovine spermatozoa. Oxygen consumption in heparin-capacitated spermatozoa was significantly higher than in hyaluronic acid-treated spermatozoa. With all treatments, mitochondrial coupling was observed when a specific uncoupler of the respiratory chain was added. The inhibition of membrane-associated adenylate cyclase significantly blocked capacitation induction produced by hyaluronic acid, maintaining a basal sperm oxygen uptake in contrast to heparin effect in which both sperm parameters were inhibited, suggesting that the membrane-associated adenylate cyclase activation is involved in the intracellular signal mechanisms induced by both capacitation inductors, but only regulates mitochondrial oxidative phosphorylation in heparin-capacitated spermatozoa.

  19. Porous NiCo2O4 nanosheets/reduced graphene oxide composite: facile synthesis and excellent capacitive performance for supercapacitors.

    PubMed

    Ma, Lianbo; Shen, Xiaoping; Ji, Zhenyuan; Cai, Xiaoqing; Zhu, Guoxing; Chen, Kangmin

    2015-02-15

    A composite with porous NiCo2O4 nanosheets attached on reduced graphene oxide (RGO) sheets is synthesized through a facile solution-based method combined with a simple thermal annealing process. The capacitive performances of the as-prepared NiCo2O4/RGO (NCG) composites as electrode materials are investigated. It is found that the NCG composites exhibit a high specific capacitance up to 1186.3 F g(-1) at the current density of 0.5 A g(-1), and superior cycling stability with about 97% of the initial capacitance after 100 cycles. The greatly enhanced capacitive performance of the NCG electrode can be attributed to the existence of RGO support, which serves as both conductive channels and active interface. The approach used in the synthesis provides a facile route for preparing graphene-binary metal oxide electrode materials. The remarkable capacitive performance of NCG composites will undoubtedly make them be attractive for high performance energy storage applications.

  20. Oligomycin A-induced inhibition of mitochondrial ATP-synthase activity suppresses boar sperm motility and in vitro capacitation achievement without modifying overall sperm energy levels.

    PubMed

    Ramió-Lluch, Laura; Yeste, Marc; Fernández-Novell, Josep M; Estrada, Efrén; Rocha, Luiz; Cebrián-Pérez, José A; Muiño-Blanco, Teresa; Concha, Ilona I; Ramírez, Alfredo; Rodríguez-Gil, Joan E

    2014-01-01

    Incubation of boar spermatozoa in a capacitation medium with oligomycin A, a specific inhibitor of the F0 component of the mitochondrial ATP synthase, induced an immediate and almost complete immobilisation of cells. Oligomycin A also inhibited the ability of spermatozoa to achieve feasible in vitro capacitation (IVC), as measured through IVC-compatible changes in motility patterns, tyrosine phosphorylation levels of the acrosomal p32 protein, membrane fluidity and the ability of spermatozoa to achieve subsequent, progesterone-induced in vitro acrosome exocytosis (IVAE). Both inhibitory effects were caused without changes in the rhythm of O2 consumption, intracellular ATP levels or mitochondrial membrane potential (MMP). IVAE was accompanied by a fast and intense peak in O2 consumption and ATP levels in control spermatozoa. Oligomycin A also inhibited progesterone-induced IVAE as well as the concomitant peaks of O2 consumption and ATP levels. The effect of oligomycin on IVAE was also accompanied by concomitant alterations in the IVAE-induced changes on intracellular Ca(2+) levels and MMP. Our results suggest that the oligomycin A-sensitive mitochondrial ATP-synthase activity is instrumental in the achievement of an adequate boar sperm motion pattern, IVC and IVAE. However, this effect seems not to be linked to changes in the overall maintenance of adequate energy levels in stages other than IVAE.

  1. All-solid-state reduced graphene oxide supercapacitor with large volumetric capacitance and ultralong stability prepared by electrophoretic deposition method.

    PubMed

    Wang, Mei; Duong, Le Dai; Mai, Nguyen Thi; Kim, Sanghoon; Kim, Youngjun; Seo, Heewon; Kim, Ye Chan; Jang, Woojin; Lee, Youngkwan; Suhr, Jonghwan; Nam, Jae-Do

    2015-01-21

    Portable energy storage devices have gained special attention due to the growing demand for portable electronics. Herein, an all-solid-state supercapacitor is successfully fabricated based on a poly(vinyl alcohol)-H3PO4 (PVA-H3PO4) polymer electrolyte and a reduced graphene oxide (RGO) membrane electrode prepared by electrophoretic deposition (EPD). The RGO electrode fabricated by EPD contains an in-plane layer-by-layer alignment and a moderate porosity that accommodate the electrolyte ions. The all-solid-state RGO supercapacitor is thoroughly tested to give high specific volumetric capacitance (108 F cm(-3)) and excellent energy and power densities (7.5 Wh cm(-3) and 2.9 W cm(-3), respectively). In addition, the all-solid-state RGO supercapacitor exhibits an ultralong lifetime for as long as 180 days (335 000 cycles), which is an ultrahigh cycling capability for a solid-state supercapacitor. The RGO is also tested for being used as a transparent supercapacitor electrode demonstrating its possible use in various transparent optoelectronic devices. Due to the facile scale-up capability of the EPD process and RGO dispersion, the developed all-solid-state supercapacitor is highly applicable to large-area portable energy storage devices.

  2. One-Dimensional Assembly of Conductive and Capacitive Metal Oxide Electrodes for High-Performance Asymmetric Supercapacitors.

    PubMed

    Harilal, Midhun; Vidyadharan, Baiju; Misnon, Izan Izwan; Anilkumar, Gopinathan M; Lowe, Adrian; Ismail, Jamil; Yusoff, Mashitah M; Jose, Rajan

    2017-03-29

    A one-dimensional morphology comprising nanograins of two metal oxides, one with higher electrical conductivity (CuO) and the other with higher charge storability (Co3O4), is developed by electrospinning technique. The CuO-Co3O4 nanocomposite nanowires thus formed show high specific capacitance, high rate capability, and high cycling stability compared to their single-component nanowire counterparts when used as a supercapacitor electrode. Practical symmetric (SSCs) and asymmetric (ASCs) supercapacitors are fabricated using commercial activated carbon, CuO, Co3O4, and CuO-Co3O4 composite nanowires, and their properties are compared. A high energy density of ∼44 Wh kg(-1) at a power density of 14 kW kg(-1) is achieved in CuO-Co3O4 ASCs employing aqueous alkaline electrolytes, enabling them to store high energy at a faster rate. The current methodology of hybrid nanowires of various functional materials could be applied to extend the performance limit of diverse electrical and electrochemical devices.

  3. The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior and Metabolite-Mediated Inhibition.

    PubMed

    Lo, Sheng-Nan; Shen, Chien-Chang; Chang, Chia-Yu; Tsai, Keng-Chang; Huang, Chiung-Chiao; Wu, Tian-Shung; Ueng, Yune-Fang

    2015-07-01

    The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a variety of pharmacological effects, such as anti-inflammation and lipid-lowering effects. Berberine causes potent CYP1B1 inhibition, whereas CYP1A2 shows resistance to the inhibition. To reveal the influence of oxidative metabolism on CYP1 inhibition by berberine, berberine oxidation and the metabolite-mediated inhibition were determined. After NADPH-fortified preincubation of berberine with P450, the inhibition of CYP1A1 and CYP1B1 variants (CYP1B1.1, CYP1B1.3, and CYP1B1.4) by berberine was not enhanced, and CYP1A2 remained resistant. Demethyleneberberine was identified as the most abundant metabolite of CYP1A1- and CYP1B1-catalyzed oxidations, and thalifendine was generated at a relatively low rate. CYP1A1-catalyzed berberine oxidation had the highest maximal velocity (V max) and exhibited positive cooperativity, suggesting the assistance of substrate binding when the first substrate was present. In contrast, the demethylenation by CYP1B1 showed the property of substrate inhibition. CYP1B1-catalyzed berberine oxidation had low K m values, but it had V max values less than 8% of those of CYP1A1. The dissociation constants generated from the binding spectrum and fluorescence quenching suggested that the low K m values of CYP1B1-catalyzed oxidation might include more than the rate constants describing berberine binding. The natural protoberberine/berberine fmetabolites with methylenedioxy ring-opening (palmatine, jatrorrhizine, and demethyleneberberine) and the demethylation (thalifendine and berberrubine) caused weak CYP1 inhibition. These results demonstrated that berberine was not efficiently oxidized by CYP1B1, and metabolism-dependent irreversible inactivation was minimal. Metabolites of berberine caused a relatively weak inhibition of CYP1.

  4. Investigating the Influence of Metal Oxide Coatings on the Properties and Performance of Carbon Electrodes in Capacitive Deionization

    NASA Astrophysics Data System (ADS)

    Wouters, Jesse J.

    Capacitive deionization (CDI) is an emerging water treatment technology that utilizes an electrochemical process to remove ions from water. More precisely, a potential is applied between a pair of electrodes and as salt water passes between the electrodes cations are removed on the negative electrode and anions on the positive. Typically, electrode materials used in CDI are porous high surface area carbons. This dissertation focuses on evaluating different carbon materials, coated with a submicron film of either SiO2 or Al 2O3, as electrodes in CDI. Moreover, a large fraction of this study is devoted to characterizing the carbon/metal oxide composites; the properties examined include: microstructure at the micro/nano scale (SEM imaging, specific surface area and pore size distribution), quantity of metal oxide deposited and wettability. In addition, the composite and uncoated carbon electrodes were also submitted to electrochemical methods of analysis: cyclic voltammetry, galvanostatic charge/discharge and constant potential CDI testing. It was found that the influence of the coatings on the properties of the electrode, were dependent on the properties of the carbon substrate. For instance, for a low surface area carbon (less than 2 m2/g) the coated composite had a specific surface area several times larger than that of uncoated carbon. However, composites produced from a high surface area carbon (greater than 1400 m2/g) with large quantities of metal oxides deposited, had specific surface areas lower than the carbon support. Likewise, the influence of the coatings on the electrochemical properties of the electrode also appeared to be dependent on the properties of the carbon support. For example, CDI testing showed increased cation removal for 3 of the 4 carbons tested when coated with SiO2; and 2 of the 4 carbons had improved anion removal when coated with Al2O3. This effect is likely due to the formation of new surface groups and/or improvements in the

  5. Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.

    PubMed

    Pakavathkumar, Prateep; Sharma, Gyanesh; Kaushal, Vikas; Foveau, Bénédicte; LeBlanc, Andrea C

    2015-09-24

    Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via the oxidation of their active site cysteine. Methylene blue, and derivatives, azure A and azure B competitively inhibited recombinant Caspase-6 (Casp6), and inhibited Casp6 activity in transfected human colon carcinoma cells and in serum-deprived primary human neuron cultures. Methylene blue also inhibited recombinant Casp1 and Casp3. Furthermore, methylene blue inhibited Casp3 activity in an acute mouse model of liver toxicity. Mass spectrometry confirmed methylene blue and azure B oxidation of the catalytic Cys163 cysteine of Casp6. Together, these results show a novel inhibitory mechanism of caspases via sulfenation of the active site cysteine. These results indicate that methylene blue or its derivatives could (1) have an additional effect against Alzheimer Disease by inhibiting brain caspase activity, (2) be used as a drug to prevent caspase activation in other conditions, and (3) predispose chronically treated individuals to cancer via the inhibition of caspases.

  6. Alpha-1-antitrypsin inhibits nitric oxide production.

    PubMed

    Chan, Edward D; Pott, Gregory B; Silkoff, Philip E; Ralston, Annemarie H; Bryan, Courtney L; Shapiro, Leland

    2012-12-01

    NO is an endogenously produced gas that regulates inflammation, vascular tone, neurotransmission, and immunity. NO production can be increased by exposing cells to several endogenous and exogenous proinflammatory mediators, including IFN-γ, TNF-α, IL-1β, and LPS. As AAT has been shown to inhibit cell activation and suppress cytokine production associated with proinflammatory stimulation, we examined AAT for NO-suppressive function. In RAW 264.7 murine macrophagic cells, physiological AAT concentrations significantly inhibited combined LPS- and IFN-γ-induced NO synthesis, and NO synthesis inhibition was associated with decreased expression of iNOS, suppressed NF-κB activation, and reduced translocation of extracellular AAT into the interior of RAW 264.7 cells. CE-2072, a synthetic inhibitor of serine proteases, also suppressed NO production, iNOS expression, and NF-κB activation. However, AAT did not alter activation of intracellular MAPKs. In subjects with genetic AAT deficiency, exhaled NO was increased significantly compared with exhaled NO in healthy controls. These in vitro and in vivo studies suggest that AAT is an endogenous inhibitor of NO production. Administering AAT or AAT-like molecules may have use as a treatment for diseases associated with excessive NO production.

  7. High-Performance Capacitive Deionization Disinfection of Water with Graphene Oxide-graft-Quaternized Chitosan Nanohybrid Electrode Coating.

    PubMed

    Wang, Yilei; El-Deen, Ahmed G; Li, Peng; Oh, Bernice H L; Guo, Zanru; Khin, Mya Mya; Vikhe, Yogesh S; Wang, Jing; Hu, Rebecca G; Boom, Remko M; Kline, Kimberly A; Becker, David L; Duan, Hongwei; Chan-Park, Mary B

    2015-10-27

    Water disinfection materials should ideally be broad-spectrum-active, nonleachable, and noncontaminating to the liquid needing sterilization. Herein, we demonstrate a high-performance capacitive deionization disinfection (CDID) electrode made by coating an activated carbon (AC) electrode with cationic nanohybrids of graphene oxide-graft-quaternized chitosan (GO-QC). Our GO-QC/AC CDID electrode can achieve at least 99.9999% killing (i.e., 6 log reduction) of Escherichia coli in water flowing continuously through the CDID cell. Without the GO-QC coating, the AC electrode alone cannot kill the bacteria and adsorbs a much smaller fraction (<82.8 ± 1.8%) of E. coli from the same biocontaminated water. Our CDID process consists of alternating cycles of water disinfection followed by electrode regeneration, each a few minutes duration, so that this water disinfection process can be continuous and it only needs a small electrode voltage (2 V). With a typical brackish water biocontamination (with 10(4) CFU mL(-1) bacteria), the GO-QC/AC electrodes can kill 99.99% of the E. coli in water for 5 h. The disinfecting GO-QC is securely attached on the AC electrode surface, so that it is noncontaminating to water, unlike many other chemicals used today. The GO-QC nanohybrids have excellent intrinsic antimicrobial properties in suspension form. Further, the GO component contributes toward the needed surface conductivity of the CDID electrode. This CDID process offers an economical method toward ultrafast, contaminant-free, and continuous killing of bacteria in biocontaminated water. The proposed strategy introduces a green in situ disinfectant approach for water purification.

  8. Low-temperature CO oxidation over a ternary oxide catalyst with high resistance to hydrocarbon inhibition

    DOE PAGES

    Binder, Andrew J.; Toops, Todd J.; Unocic, Raymond R.; ...

    2015-09-11

    Platinum group metal (PGM) catalysts are the current standard for control of pollutants in automotive exhaust streams. Aside from their high cost, PGM catalysts struggle with CO oxidation at low temperatures (<200 °C) due to inhibition by hydrocarbons in exhaust streams. Here we present a ternary mixed oxide catalyst composed of copper oxide, cobalt oxide, and ceria (dubbed CCC) that outperforms synthesized and commercial PGM catalysts for CO oxidation in simulated exhaust streams while showing no signs of inhibition by propene. Diffuse reflectance IR (DRIFTS) and light-off data both indicate low interaction between propene and the CO oxidation active sitemore » on this catalyst, and a separation of adsorption sites is proposed as the cause of this inhibition resistance. In conclusion, this catalyst shows great potential as a low-cost component for low temperature exhaust streams that are expected to be a characteristic of future automotive systems.« less

  9. Low-temperature CO oxidation over a ternary oxide catalyst with high resistance to hydrocarbon inhibition

    SciTech Connect

    Binder, Andrew J.; Toops, Todd J.; Unocic, Raymond R.; Parks, II, James E.; Dai, Sheng

    2015-09-11

    Platinum group metal (PGM) catalysts are the current standard for control of pollutants in automotive exhaust streams. Aside from their high cost, PGM catalysts struggle with CO oxidation at low temperatures (<200 °C) due to inhibition by hydrocarbons in exhaust streams. Here we present a ternary mixed oxide catalyst composed of copper oxide, cobalt oxide, and ceria (dubbed CCC) that outperforms synthesized and commercial PGM catalysts for CO oxidation in simulated exhaust streams while showing no signs of inhibition by propene. Diffuse reflectance IR (DRIFTS) and light-off data both indicate low interaction between propene and the CO oxidation active site on this catalyst, and a separation of adsorption sites is proposed as the cause of this inhibition resistance. In conclusion, this catalyst shows great potential as a low-cost component for low temperature exhaust streams that are expected to be a characteristic of future automotive systems.

  10. Nitric Oxide Inhibits Coxiella burnetii Replication and Parasitophorous Vacuole Maturation

    PubMed Central

    Howe, Dale; Barrows, Lorraine F.; Lindstrom, Nicole M.; Heinzen, Robert A.

    2002-01-01

    Nitric oxide is a recognized cytotoxic effector against facultative and obligate intracellular bacteria. This study examined the effect of nitric oxide produced by inducible nitric oxide synthase (iNOS) up-regulated in response to cytokine stimulation, or by a synthetic nitric oxide donor, on replication of obligately intracellular Coxiella burnetii in murine L-929 cells. Immunoblotting and nitrite assays revealed that C. burnetii infection of L-929 cells augments expression of iNOS up-regulated in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Infection in the absence of cytokine stimulation did not result in demonstrable up-regulation of iNOS expression or in increased nitrite production. Nitrite production by cytokine-treated cells was significantly inhibited by the iNOS inhibitor S-methylisothiourea (SMT). Treatment of infected cells with IFN-γ and TNF-α or the synthetic nitric oxide donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NONOate) had a bacteriostatic effect on C. burnetii replication. Inhibition of replication was reversed upon addition of SMT to the culture medium of cytokine-treated cells. Microscopic analysis of infected cells revealed that nitric oxide (either cytokine induced or donor derived) inhibited formation of the mature (large) parasitophorous vacuole that is characteristic of C. burnetii infection of host cells. Instead, exposure of infected cells to nitric oxide resulted in the formation of multiple small, acidic vacuoles usually containing one C. burnetii cell. Removal of nitrosative stress resulted in the coalescence of small vacuoles to form a large vacuole harboring multiple C. burnetii cells. These experiments demonstrate that nitric oxide reversibly inhibits replication of C. burnetii and formation of the parasitophorous vacuole. PMID:12183564

  11. Design and Development for Capacitive Humidity Sensor Applications of Lead-Free Ca,Mg,Fe,Ti-Oxides-Based Electro-Ceramics with Improved Sensing Properties via Physisorption

    PubMed Central

    Tripathy, Ashis; Pramanik, Sumit; Manna, Ayan; Bhuyan, Satyanarayan; Azrin Shah, Nabila Farhana; Radzi, Zamri; Abu Osman, Noor Azuan

    2016-01-01

    Despite the many attractive potential uses of ceramic materials as humidity sensors, some unavoidable drawbacks, including toxicity, poor biocompatibility, long response and recovery times, low sensitivity and high hysteresis have stymied the use of these materials in advanced applications. Therefore, in present investigation, we developed a capacitive humidity sensor using lead-free Ca,Mg,Fe,Ti-Oxide (CMFTO)-based electro-ceramics with perovskite structures synthesized by solid-state step-sintering. This technique helps maintain the submicron size porous morphology of the developed lead-free CMFTO electro-ceramics while providing enhanced water physisorption behaviour. In comparison with conventional capacitive humidity sensors, the presented CMFTO-based humidity sensor shows a high sensitivity of up to 3000% compared to other materials, even at lower signal frequency. The best also shows a rapid response (14.5 s) and recovery (34.27 s), and very low hysteresis (3.2%) in a 33%–95% relative humidity range which are much lower values than those of existing conventional sensors. Therefore, CMFTO nano-electro-ceramics appear to be very promising materials for fabricating high-performance capacitive humidity sensors. PMID:27455263

  12. Analysis of amorphous indium-gallium-zinc-oxide thin-film transistor contact metal using Pilling-Bedworth theory and a variable capacitance diode model

    NASA Astrophysics Data System (ADS)

    Kiani, Ahmed; Hasko, David G.; Milne, William I.; Flewitt, Andrew J.

    2013-04-01

    It is widely reported that threshold voltage and on-state current of amorphous indium-gallium-zinc-oxide bottom-gate thin-film transistors are strongly influenced by the choice of source/drain contact metal. Electrical characterisation of thin-film transistors indicates that the electrical properties depend on the type and thickness of the metal(s) used. Electron transport mechanisms and possibilities for control of the defect state density are discussed. Pilling-Bedworth theory for metal oxidation explains the interaction between contact metal and amorphous indium-gallium-zinc-oxide, which leads to significant trap formation. Charge trapping within these states leads to variable capacitance diode-like behavior and is shown to explain the thin-film transistor operation.

  13. Inhibition of catalytic oxidation of carbon/carbon composite materials

    NASA Astrophysics Data System (ADS)

    Wu, Xianxian

    An investigation coupling experimental efforts with computational chemistry analysis was conducted to study the inhibition effects of phosphorous or boron on the oxidation of carbon/carbon composite materials catalyzed by potassium or calcium acetate (KAC or CaAC). Commercial aircraft brakes were used, which are exposed during use to K- or Ca-containing runway deicing agents. The reactivity of inhibitor-doped carbon materials was determined by temperature programmed oxidation (TPO) and isothermal oxidation in 1 atm O2. The structure and surface chemistry of inhibitor-doped samples were characterized, and the inhibition mechanisms were explored with the help of ab initio molecular orbital calculations. The catalytic effects of KAC or CaAC were found to be dependent on catalyst loading, pretreatment procedure, temperature and O2 partial pressure. Experimental observations showed that K is a more effective catalyst for carbon composite oxidation than Ca as expected from prior studies of catalyzed carbon gasification. This was attributed to its ability to form and maintain good interfacial contact with carbon, as well as to its insensitivity to carbon structure because of its excellent wetting ability and mobility. The experimental results suggested that the interfacial catalyst/carbon contact is the critical factor determining the catalytic effectiveness. Thermally deposited phosphorus, upon heat treatment of P-containing compounds such as CH3OP(OH)2 and POCl3 at around 600°C in the presence of inert gas, exhibited a good inhibition effect in the oxidation of C/C composites used in aircraft brake systems. These P compounds were also effective inhibitors for Ca- or K-catalyzed oxidation. The P loading up to a certain amount (ca. 4.0 wt%) was found to suppress Ca-catalyzed oxidation completely. It also improved the resistance of carbon to K-catalyzed oxidation, but the effect was much less significant than in the case of Ca-catalyzed reaction. The characterization of P

  14. Difference in chemical reactions in bulk plasma and sheath regions during surface modification of graphene oxide film using capacitively coupled NH{sub 3} plasma

    SciTech Connect

    Lee, Sung-Youp; Kim, Chan; Kim, Hong Tak

    2015-09-14

    Reduced graphene oxide (r-GO) films were obtained from capacitively coupled NH{sub 3} plasma treatment of spin-coated graphene oxide (GO) films at room temperature. Variations were evaluated according to the two plasma treatment regions: the bulk plasma region (R{sub bulk}) and the sheath region (R{sub sheath}). Reduction and nitridation of the GO films began as soon as the NH{sub 3} plasma was exposed to both regions. However, with the increase in treatment time, the reduction and nitridation reactions differed in each region. In the R{sub bulk}, NH{sub 3} plasma ions reacted chemically with oxygen functional groups on the GO films, which was highly effective for reduction and nitridation. While in the R{sub sheath}, physical reactions by ion bombardment were dominant because plasma ions were accelerated by the strong electrical field. The accelerated plasma ions reacted not only with the oxygen functional groups but also with the broken carbon chains, which caused the removal of the GO films by the formation of hydrocarbon gas species. These results showed that reduction and nitridation in the R{sub bulk} using capacitively coupled NH{sub 3} plasma were very effective for modifying the properties of r-GO films for application as transparent conductive films.

  15. Taurine inhibition of metal-stimulated catecholamine oxidation.

    PubMed

    Dawson, R; Baker, D; Eppler, B; Tang, E; Shih, D; Hern, H; Hu, M

    2000-01-01

    Taurine is an abundant amino acid found in mammalian tissues and it has been suggested to have cytoprotective functions. The aim of the present study was to determine if taurine had the potential to reduce oxidative stress associated with metal-stimulated catecholamine oxidation. Taurine and structural analogs of taurine were tested for their ability to inhibit metal-stimulated quinone formation from dopamine or L-dopa. Oxidative damage to proteins and lipids were also assessed in vitro and the effects of taurine were determined. Taurine (20 mM) was found to decrease significantly ferric iron (50-500 microM)- and manganese (10 microM)-stimulated L-dopa or dopamine oxidation. Taurine had no effect on zinc-induced dopamine oxidation and slightly potentiated copper- and NaIO(4)-stimulated quinone formation. Ferric iron-stimulated lipid peroxidation was not affected by taurine (1-20 mM). Protein carbonyl formation induced by ferric iron (500 microM) and L-dopa (500 microM) was significantly reduced by 10 mM taurine. The cytotoxicity of L-dopa (250 microM) and ferric chloride (75 microM) to LLC-PK(1) cells was attenuated by 10 mM taurine or hypotaurine. Homotaurine alone stimulated L-dopa oxidation and potentiated the cytotoxic effects of ferric iron. Homotaurine was found to be cytotoxic when combined with L-dopa or L-dopa/iron. In contrast, hypotaurine inhibited quinone formation and protected LLC-PK(1) cells. These studies suggest that taurine may exhibit cytoprotective effects against the oxidation products of catecholamines by acting as a scavenger for free radicals and cytotoxic quinones.

  16. AIF inhibits tumor metastasis by protecting PTEN from oxidation

    PubMed Central

    Shen, Shao-Ming; Guo, Meng; Xiong, Zhong; Yu, Yun; Zhao, Xu-Yun; Zhang, Fei-Fei; Chen, Guo-Qiang

    2015-01-01

    Apoptosis-inducing factor (AIF) exerts dual roles on cell death and survival, but its substrates as a putative oxidoreductase and roles in tumorigenesis remain elusive. Here, we report that AIF physically interacts with and inhibits the oxidation of phosphatase and tensin homolog on chromosome ten (PTEN), a tumor suppressor susceptible for oxidation-mediated inactivation. More intriguingly, we also identify PTEN as a mitochondrial protein and the ectopic expression of mitochondrial targeting sequence-carrying PTEN almost completely inhibits Akt phosphorylation in PTEN-deficient cells. AIF knockdown causes oxidation-mediated inactivation of the lipid phosphatase activity of PTEN, with ensuing activation of Akt kinase, phosphorylation of the Akt substrate GSK-3β, and activation of β-catenin signaling in cancer cells. Through its effect on β-catenin signaling, AIF inhibits epithelial–mesenchymal transition (EMT) and metastasis of cancer cells in vitro and in orthotopically implanted xenografts. Accordingly, the expression of AIF is correlated with the survival of human patients with cancers of multiple origins. These results identify PTEN as the substrate of AIF oxidoreductase and reveal a novel function for AIF in controlling tumor metastasis. PMID:26415504

  17. Oxidative stress inhibits distant metastasis by human melanoma cells

    PubMed Central

    Piskounova, Elena; Agathocleous, Michalis; Murphy, Malea M.; Hu, Zeping; Huddlestun, Sara E.; Zhao, Zhiyu; Leitch, A. Marilyn; Johnson, Timothy M.; DeBerardinis, Ralph J.; Morrison, Sean J.

    2015-01-01

    Solid cancer cells commonly enter the blood and disseminate systemically but are highly inefficient at forming distant metastases for poorly understood reasons. We studied human melanomas that differed in their metastasis histories in patients and in their capacity to metastasize in NSG mice. All melanomas had high frequencies of cells that formed subcutaneous tumours, but much lower percentages of cells that formed tumours after intravenous or intrasplenic transplantation, particularly among inefficient metastasizers. Melanoma cells in the blood and visceral organs experienced oxidative stress not observed in established subcutaneous tumours. Successfully metastasizing melanomas underwent reversible metabolic changes during metastasis that increased their capacity to withstand oxidative stress, including increased dependence upon NADPH-generating enzymes in the folate pathway. Anti-oxidants promoted distant metastasis in NSG mice. Folate pathway inhibition using low-dose methotrexate, ALDH1L2 knockdown, or MTHFD1 knockdown inhibited distant metastasis without significantly affecting the growth of subcutaneous tumors in the same mice. Oxidative stress thus limits distant metastasis by melanoma cells in vivo. PMID:26466563

  18. Inhibition of arm regeneration by Ophioderma brevispina (Echinodermata, Ophiuroidea) by tributyltin oxide and triphenyltin oxide

    SciTech Connect

    Walsh, G.E.; McLaughlin, L.L.; Louie, M.K.; Deans, C.H.; Lores, E.M.

    1986-08-01

    Effects of water-bourne toxicants on regeneration of arms by the brittle star, Ophioderma brevispina, are described. Regeneration was inhibited by 0.1 micrograms liter-1 bis(tri-n-butyltin)oxide and bis(triphenyltin)oxide. Both substances are known to act upon the nervous system, and it is suggested that inhibition was caused by neurotoxicological action of the tin compounds or by their direct effect upon tissue at the breakage point. The former is most likely because regeneration is mediated by the radial nerves of brittle stars.

  19. Nitric oxide inhibition of coxsackievirus replication in vitro.

    PubMed Central

    Zaragoza, C; Ocampo, C J; Saura, M; McMillan, A; Lowenstein, C J

    1997-01-01

    Nitric oxide is a radical molecule with antibacterial, -parasitic, and -viral properties. We investigated the mechanism of NO inhibition of Coxsackievirus B3 (CVB3) replication in vitro by determining the effect of NO upon a single replicative cycle of CVB3 grown in HeLa cells. Transfection of inducible NO synthase cDNA into HeLa cells reduces the number of viral particles produced during a single cycle of growth. Similarly, a noncytotoxic concentration of the NO donor S-nitroso-amino-penicillamine reduces the number of viral particles in a dose-dependent manner. To explore the mechanisms by which NO exerts its antiviral effect, we assayed the attachment, replication, and translation steps of the CVB3 life cycle. NO does not affect the attachment of CVB3 to HeLa cells. However, NO inhibits CVB3 RNA synthesis, as shown by a [3H]uridine incorporation assay, reverse transcription-PCR, and Northern analysis. In addition, NO inhibits CVB3 protein synthesis, as shown by [35S]methionine protein labeling and Western blot analysis of infected cells. Thus, NO inhibits CVB3 replication in part by inhibiting viral RNA synthesis by an unknown mechanism. PMID:9312175

  20. Quercetin inhibited cadmium-induced autophagy in the mouse kidney via inhibition of oxidative stress

    PubMed Central

    Yuan, Yuan; Ma, Shixun; Qi, Yongmei; Wei, Xue; Cai, Hui; Dong, Li; Lu, Yufeng; Zhang, Yupeng; Guo, Qingjin

    2016-01-01

    The objective of the current study was to explore the inhibitory effects of quercetin on cadmium-induced autophagy in mouse kidneys. Mice were intraperitoneally injected with cadmium and quercetin once daily for 3 days. The LC3-II/β-actin ratio was used as the autophagy marker, and autophagy was observed by transmission electron microscopy. Oxidative stress was investigated in terms of reactive oxygen species, total antioxidant capacity, and malondialdehyde. Cadmium significantly induced typical autophagosome formation, increased the LC3-II/β-actin ratio, reactive oxygen species level, and malondialdehyde content, and decreased total antioxidant capacity. Interestingly, quercetin markedly decreased the cadmium-induced LC3-II/β-actin ratio, reactive oxygen species levels, and malondialdehyde content, and simultaneously increased total antioxidant capacity. Cadmium can inhibit total antioxidant capacity, produce a large amount of reactive oxygen species, lead to oxidative stress, and promote lipid peroxidation, eventually inducing autophagy in mouse kidneys. Quercetin could inhibit cadmium-induced autophagy via inhibition of oxidative stress. This study may provide a theoretical basis for the treatment of cadmium injury. PMID:27821909

  1. Contact resistance and overlapping capacitance in flexible sub-micron long oxide thin-film transistors for above 100 MHz operation

    NASA Astrophysics Data System (ADS)

    Münzenrieder, Niko; Salvatore, Giovanni A.; Petti, Luisa; Zysset, Christoph; Büthe, Lars; Vogt, Christian; Cantarella, Giuseppe; Tröster, Gerhard

    2014-12-01

    In recent years new forms of electronic devices such as electronic papers, flexible displays, epidermal sensors, and smart textiles have become reality. Thin-film transistors (TFTs) are the basic blocks of the circuits used in such devices and need to operate above 100 MHz to efficiently treat signals in RF systems and address pixels in high resolution displays. Beyond the choice of the semiconductor, i.e., silicon, graphene, organics, or amorphous oxides, the junctionless nature of TFTs and its geometry imply some limitations which become evident and important in devices with scaled channel length. Furthermore, the mechanical instability of flexible substrates limits the feature size of flexible TFTs. Contact resistance and overlapping capacitance are two parasitic effects which limit the transit frequency of transistors. They are often considered independent, while a deeper analysis of TFTs geometry imposes to handle them together; in fact, they both depend on the overlapping length (LOV) between source/drain and the gate contacts. Here, we conduct a quantitative analysis based on a large number of flexible ultra-scaled IGZO TFTs. Devices with three different values of overlap length and channel length down to 0.5 μm are fabricated to experimentally investigate the scaling behavior of the transit frequency. Contact resistance and overlapping capacitance depend in opposite ways on LOV. These findings establish routes for the optimization of the dimension of source/drain contact pads and suggest design guidelines to achieve megahertz operation in flexible IGZO TFTs and circuits.

  2. Inhibition of Frying Oil Oxidation by Carbon Dioxide Blanketing.

    PubMed

    Totani, Nagao; Inoue, Ryota; Yawata, Miho

    2016-06-01

    The oxidation of oil starts, in general, from the penetration of atmospheric oxygen into oil. Inhibition of the vigorous oxidation of oil at deep-frying temperature under carbon dioxide flow, by disrupting the contact between oil and air, was first demonstrated using oil in a round bottom flask. Next, the minimum carbon dioxide flow rate necessary to blanket 4 L of frying oil in an electric fryer (surface area 690 cm(2)) installed with nonwoven fabric cover, was found to be 40 L/h. Then deep-frying of potato was done accordingly; immediately after deep-frying, an aluminum cover was placed on top of the nonwoven fabric cover to prevent the loss of carbon dioxide and the carbon dioxide flow was shut off. In conclusion, the oxidation of oil both at deep-frying temperature and during standing was remarkably inhibited by carbon dioxide blanketing at a practical flow rate and volume. Under the deep-frying conditions employed in this study, the increase in polar compound content was reduced to half of that of the control.

  3. Inhibition of Sulfide Mineral Oxidation by Surface Coating Agents: Batch

    NASA Astrophysics Data System (ADS)

    Choi, J.; Ji, M. K.; Yun, H. S.; Park, Y. T.; Gee, E. D.; Lee, W. R.; Jeon, B.-H.

    2012-04-01

    Mining activities and mineral industries have impacted on rapid oxidation of sulfide minerals such as pyrite (FeS2) which leads to Acid Mine Drainage (AMD) formation. Some of the abandoned mines discharge polluted water without proper environmental remediation treatments, largely because of financial constraints in treating AMD. Magnitude of the problem is considerable, especially in countries with a long history of mining. As metal sulfides become oxidized during mining activities, the aqueous environment becomes acid and rich in many metals, including iron, lead, mercury, arsenic and many others. The toxic heavy metals are responsible for the environmental deterioration of stream, groundwater and soils. Several strategies to remediate AMD contaminated sites have been proposed. Among the source inhibition and prevention technologies, microencapsulation (coating) has been considered as a promising technology. The encapsulation is based on inhibition of O2 diffusion by surface coating agent and is expected to control the oxidation of pyrite for a long time. Potential of several surface coating agents for preventing oxidation of metal sulfide minerals from both Young-Dong coal mine and Il-Gwang gold mine were examined by conducting batch experiments and field tests. Powdered pyrite as a standard sulfide mineral and rock samples from two mine outcrops were mixed with six coating agents (KH2PO4, MgO and KMnO4 as chemical agents, and apatite, cement and manganite as mineral agents) and incubated with oxidizing agents (H2O2 or NaClO). Batch experiments with Young-Dong coal mine samples showed least SO42- production in presence of KMnO4 (16% sulfate production compared to no surface coating agents) or cement (4%) within 8 days. In the case of Il-Gwang mine samples, least SO42- production was observed in presence of KH2PO4 (8%) or cement (2%) within 8 days. Field-scale pilot tests at Il-Gwang site also showed that addition of KH2PO4 decreased sulfate production from 200 to

  4. Taylor expansions of band-bending in MOS capacitance: application to scanning capacitance microscopy

    NASA Astrophysics Data System (ADS)

    Murray, Hugues; Martin, Patrick; Bardy, Serge; Murray, Franck

    2008-03-01

    The differential capacitance C(Vg) = dQM/dVg in a metal-oxide-semiconductor structure introduces the silicon capacitance Cs(ΨS) = -dQS/dΨS depending on the surface band-bending ΨS at the oxide-semiconductor interface. In order to calculate the dependence of Cs on the gate voltage Vg, we propose in this paper a simple numerical method, based on first-order Taylor expansions, to inverse the explicit equation Vg = f(ΨS). This method is then applied to calculate the analytic differential capacitance of the scanning capacitance microscope (SCM) in all conditions relative to physical parameters of SCM such as oxide thickness, doping profiles and probe erosion. It results in a competitive tool for SCM users to evaluate the theoretical values of capacitance and differential capacitance in all configurations.

  5. Nitric oxide inhibits isoproterenol-stimulated adipocyte lipolysis through oxidative inactivation of the beta-agonist.

    PubMed Central

    Klatt, P; Cacho, J; Crespo, M D; Herrera, E; Ramos, P

    2000-01-01

    Nitric oxide has been implicated in the inhibition of catecholamine-stimulated lipolysis in adipose tissue by as yet unknown mechanisms. In the present study, it is shown that the nitric oxide donor, 2,2-diethyl-1-nitroso-oxyhydrazine, antagonized isoproterenol (isoprenaline)-induced lipolysis in rat adipocytes, freshly isolated from white adipose tissue, by decreasing the potency of the beta-agonist without affecting its efficacy. These data suggest that nitric oxide did not act downstream of the beta-adrenoceptor but reduced the effective concentration of isoproterenol. In support of the latter hypothesis, we found that pre-treatment of isoproterenol with nitric oxide abolished the lipolytic activity of the catecholamine. Spectroscopic data and HPLC analysis confirmed that the nitric oxide-mediated inactivation of isoproterenol was in fact because of the modification of the catecholamine through a sequence of oxidation reactions, which apparently involved the generation of an aminochrome. Similarly, aminochrome was found to be the primary product of isoproterenol oxidation by 3-morpholinosydnonimine and peroxynitrite. Finally, it was shown that nitric oxide released from cytokine-stimulated adipocytes attenuated the lipolytic effect of isoproterenol by inactivating the catecholamine. In contrast with very recent findings, which suggest that nitric oxide impairs the beta-adrenergic action of isoproterenol through intracellular mechanisms and not through a chemical reaction between NO and the catecholamine, we showed that nitric oxide was able to attenuate the pharmacological activity of isoproterenol in vitro as well as in a nitric oxide-generating cellular system through oxidation of the beta-agonist. These findings should be taken into account in both the design and interpretation of studies used to investigate the role of nitric oxide as a modulator of isoproterenol-stimulated signal transduction pathways. PMID:11023835

  6. Nitric oxide inhibits isoproterenol-stimulated adipocyte lipolysis through oxidative inactivation of the beta-agonist.

    PubMed

    Klatt, P; Cacho, J; Crespo, M D; Herrera, E; Ramos, P

    2000-10-15

    Nitric oxide has been implicated in the inhibition of catecholamine-stimulated lipolysis in adipose tissue by as yet unknown mechanisms. In the present study, it is shown that the nitric oxide donor, 2,2-diethyl-1-nitroso-oxyhydrazine, antagonized isoproterenol (isoprenaline)-induced lipolysis in rat adipocytes, freshly isolated from white adipose tissue, by decreasing the potency of the beta-agonist without affecting its efficacy. These data suggest that nitric oxide did not act downstream of the beta-adrenoceptor but reduced the effective concentration of isoproterenol. In support of the latter hypothesis, we found that pre-treatment of isoproterenol with nitric oxide abolished the lipolytic activity of the catecholamine. Spectroscopic data and HPLC analysis confirmed that the nitric oxide-mediated inactivation of isoproterenol was in fact because of the modification of the catecholamine through a sequence of oxidation reactions, which apparently involved the generation of an aminochrome. Similarly, aminochrome was found to be the primary product of isoproterenol oxidation by 3-morpholinosydnonimine and peroxynitrite. Finally, it was shown that nitric oxide released from cytokine-stimulated adipocytes attenuated the lipolytic effect of isoproterenol by inactivating the catecholamine. In contrast with very recent findings, which suggest that nitric oxide impairs the beta-adrenergic action of isoproterenol through intracellular mechanisms and not through a chemical reaction between NO and the catecholamine, we showed that nitric oxide was able to attenuate the pharmacological activity of isoproterenol in vitro as well as in a nitric oxide-generating cellular system through oxidation of the beta-agonist. These findings should be taken into account in both the design and interpretation of studies used to investigate the role of nitric oxide as a modulator of isoproterenol-stimulated signal transduction pathways.

  7. Apple juice inhibits human low density lipoprotein oxidation.

    PubMed

    Pearson, D A; Tan, C H; German, J B; Davis, P A; Gershwin, M E

    1999-01-01

    Dietary phenolic compounds, ubiquitous in vegetables and fruits and their juices possess antioxidant activity that may have beneficial effects on human health. The phenolic composition of six commercial apple juices, and of the peel (RP), flesh (RF) and whole fresh Red Delicious apples (RW), was determined by high performance liquid chromatography (HPLC), and total phenols were determined by the Folin-Ciocalteau method. HPLC analysis identified and quantified several classes of phenolic compounds: cinnamates, anthocyanins, flavan-3-ols and flavonols. Phloridzin and hydroxy methyl furfural were also identified. The profile of phenolic compounds varied among the juices. The range of concentrations as a percentage of total phenolic concentration was: hydroxy methyl furfural, 4-30%; phloridzin, 22-36%; cinnamates, 25-36%; anthocyanins, n.d.; flavan-3-ols, 8-27%; flavonols, 2-10%. The phenolic profile of the Red Delicious apple extracts differed from those of the juices. The range of concentrations of phenolic classes in fresh apple extracts was: hydroxy methyl furfural, n.d.; phloridzin, 11-17%; cinnamates, 3-27%; anthocyanins, n.d.-42%; flavan-3-ols, 31-54%; flavonols, 1-10%. The ability of compounds in apple juices and extracts from fresh apple to protect LDL was assessed using an in vitro copper catalyzed human LDL oxidation system. The extent of LDL oxidation was determined as hexanal production using static headspace gas chromatography. The apple juices and extracts, tested at 5 microM gallic acid equivalents (GAE), all inhibited LDL oxidation. The inhibition by the juices ranged from 9 to 34%, and inhibition by RF, RW and RP was 21, 34 and 38%, respectively. Regression analyses revealed no significant correlation between antioxidant activity and either total phenolic concentration or any specific class of phenolics. Although the specific components in the apple juices and extracts that contributed to antioxidant activity have yet to be identified, this study

  8. Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress.

    PubMed

    Yu, Xiao-Lin; Li, Ya-Nan; Zhang, He; Su, Ya-Jing; Zhou, Wei-Wei; Zhang, Zi-Ping; Wang, Shao-Wei; Xu, Peng-Xin; Wang, Yu-Jiong; Liu, Rui-Tian

    2015-10-01

    Recent evidence showed that amylin deposition is not only found in the pancreas in type 2 diabetes mellitus (T2DM) patients, but also in other peripheral organs, such as kidneys, heart and brain. Circulating amylin oligomers that cross the blood-brain barrier and accumulate in the brain may be an important contributor to diabetic cerebral injury and neurodegeneration. Moreover, increasing epidemiological studies indicate that there is a significant association between T2DM and Alzheimer's disease (AD). Amylin and β-amyloid (Aβ) may share common pathophysiology and show strikingly similar neurotoxicity profiles in the brain. To explore the potential effects of rutin on AD, we here investigated the effect of rutin on amylin aggregation by thioflavin T dyeing, evaluated the effect of rutin on amylin-induced neurocytotoxicity by the MTT assay, and assessed oxidative stress, as well as the generation of nitric oxide (NO) and pro-inflammatory cytokines in neuronal cells. Our results showed that the flavonoid antioxidant rutin inhibited amylin-induced neurocytotoxicity, decreased the production of reactive oxygen species (ROS), NO, glutathione disulfide (GSSG), malondialdehyde (MDA) and pro-inflammatory cytokines TNF-α and IL-1β, attenuated mitochondrial damage and increased the GSH/GSSG ratio. These protective effects of rutin may have resulted from its ability to inhibit amylin aggregation, enhance the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and reduce inducible nitric oxide synthase (iNOS) activity. These in vitro results indicate that rutin is a promising natural product for protecting neuronal cells from amylin-induced neurotoxicity and oxidative stress, and rutin administration could be a feasible therapeutic strategy for preventing AD development and protecting the aging brain or slowing neurodegenerative processes.

  9. Redox regulation of mammalian sperm capacitation

    PubMed Central

    O’Flaherty, Cristian

    2015-01-01

    Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility. PMID:25926608

  10. Trielectrode capacitive pressure transducer

    NASA Technical Reports Server (NTRS)

    Coon, G. W. (Inventor)

    1976-01-01

    A capacitive transducer and circuit especially suited for making measurements in a high-temperature environment are described. The transducer includes two capacitive electrodes and a shield electrode. As the temperature of the transducer rises, the resistance of the insulation between the capacitive electrode decreases and a resistive current attempts to interfere with the capacitive current between the capacitive electrodes. The shield electrode and the circuit coupled there reduce the resistive current in the transducer. A bridge-type circuit coupled to the transducer ignores the resistive current and measures only the capacitive current flowing between the capacitive electrodes.

  11. Oxidative Tea Polyphenols Greatly Inhibit the Absorption of Atenolol

    PubMed Central

    Shan, Yun; Zhang, Mengmeng; Wang, Tengfei; Huang, Qin; Yin, Dan; Xiang, Zemin; Wang, Xuanjun; Sheng, Jun

    2016-01-01

    Oxidative tea polyphenols (OTPs) is the oxidative polymerization product of epigallocatechin-3-O-gallate (EGCG) forms during the process of Pu-er tea fermentation, and possesses absorption property, which may absorbs on drugs thus impact the drug bioavailability when taking medicines with Pu-er tea. Here we demonstrated that OTP inhibited the absorption of atenolol in the intestine, which was determined by testing atenolol levels of plasma via high performance liquid chromatography (HPLC). After administration of atenolol (50 mg/kg), atenolol was absorbed (Tmax: 1.867 h) with the half-life (t1/2) of 6.663 h in control group; Compared with atenolol group, AUC0-t (h*ng/ml), AUC0-∞(h∗ng/ml), and Cmax of OTP+atenolol group (OTP 500 mg/kg + atenolol 50 mg/kg) reduced 38.7, 27, and 51%, respectively, the atenolol concentration of plasma was reduced by OTP approximately 43, 49, and 55.5% at 30 min, 1 and 2 h, respectively, (P < 0.01). Furthermore, the level of atenolol in feces was higher in the OTP+atenolol group, indicating that the absorption of atenolol in rats was inhibited by OTP. Isothermal titration calorimetry assay identified that EGCG can bind to atenolol and the in vitro results showed that OTP absorbed on atenolol and formed precipitate in acid condition, demonstrating a significant positive relationship between atenolol levels and OTP dosage. Taken together, these results suggested that consuming Pu-er tea with atenolol might inhibit atenolol absorption and possible other drugs. PMID:27445825

  12. Cloricromene inhibits the induction of nitric oxide synthase.

    PubMed

    Zingarelli, B; Carnuccio, R; Di Rosa, M

    1993-10-19

    The effect of cloricromene, a coumarin derivative, was investigated on the lipopolysaccharide-stimulated nitric oxide (NO) synthase induction in intact aortas from endotoxin shocked rats and in the murine macrophage cell line J774. Rings of thoracic aortas from lipopolysaccharide (4 mg/kg, i.v.)-shocked rats, contracted with phenylephrine, showed a progressive decrease in tone, that was of a greater magnitude than that of aortas from naive rats. Moreover, a decreased response to the constrictor effect of phenylephrine was observed in aortas from shocked rats. In vivo treatment with cloricromene (2 mg/kg, i.v.) 30 min before lipopolysaccharide administration partially prevented the loss in tone of aortic rings and improved their reactivity to phenylephrine. Murine J774 macrophages activated with lipopolysaccharide (100 ng/ml) produced significant amounts of nitrites (NO2-; 28.2 +/- 3.5 nmol/10(6) cells per 24 h). Cloricromene (2, 20 or 200 microM) added to the cells concomitantly with lipopolysaccharide inhibited NO2- production in a concentration-dependent manner. Maximum inhibition (84.0 +/- 8.0%) was observed when cloricromene (200 microM) was added to the cells 6 h before lipopolysaccharide, whereas it was ineffective when given 6 h after endotoxin. These results demonstrate that cloricromene inhibits the expression but not the activity of the inducible NO synthase.

  13. Inhibition of Penicillium expansum by an oxidative treatment.

    PubMed

    Cerioni, Luciana; Lazarte, María de Los Ángeles; Villegas, Josefina María; Rodríguez-Montelongo, Luisa; Volentini, Sabrina Inés

    2013-04-01

    Several oxidizing compounds such as sodium hypochlorite (NaClO) and hydrogen peroxide (H(2)O(2)) are used to control postharvest decay in fresh fruit due to their antimicrobial effects. Here, we applied these compounds in vitro, in the presence of CuSO(4), against Penicillium expansum, causal agent of apple blue mold. MICs were 50 mg L(-1) and 400 mmol L(-1) for NaClO and H(2)O(2), respectively, when these compounds were individually applied to conidia suspensions during 2 min. A combined oxidative treatment (OT) consisting on an incubation with 1 mg L(-1) NaClO and 200 mmol L(-1) H(2)O(2), in the presence of 6 mmol L(-1) CuSO(4), inhibited growth, conidial germination and fungal infectivity on apple. The fractional inhibitory concentration index for the interaction between NaClO and H(2)O(2) in the OT was 0.52 indicating a synergistic effect of the oxidizing compounds. These results suggest that the OT could be an interesting alternative for apple diseases postharvest control.

  14. Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.

    PubMed

    Schinella, Guillermo R; Tournier, Horacio A; Máñez, Salvador; de Buschiazzo, Perla M; Del Carmen Recio, María; Ríos, José Luis

    2007-01-01

    Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). In conclusion, tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol.

  15. Bioenergetics of Mammalian Sperm Capacitation

    PubMed Central

    Ferramosca, Alessandra; Zara, Vincenzo

    2014-01-01

    After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods. PMID:24791005

  16. Nitric oxide inhibits viral replication in murine myocarditis.

    PubMed Central

    Lowenstein, C J; Hill, S L; Lafond-Walker, A; Wu, J; Allen, G; Landavere, M; Rose, N R; Herskowitz, A

    1996-01-01

    Nitric oxide (NO) is a radical molecule that not only serves as a vasodilator and neurotransmitter but also acts as a cytotoxic effector molecule of the immune system. The inducible enzyme making NO, inducible NO synthase (iNOS), is transcriptionally activated by IFN-gamma and TNF-alpha, cytokines which are produced during viral infection. We show that iNOS is induced in mice infected with the Coxsackie B3 virus. Macrophages expressing iNOS are identified in the hearts and spleens of infected animals with an antibody raised against iNOS. Infected mice have increased titers of virus and a higher mortality when fed NOS inhibitors. Thus, viral infection induces iNOS in vivo, and NO inhibits viral replication. NO is a novel, nonspecific immune defense against viruses in vivo. PMID:8621766

  17. Multiple effects of 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF 96365) on Ca2+ signaling in MDCK cells: depletion of thapsigargin-sensitive Ca2+ store followed by capacitative Ca2+ entry, activation of a direct Ca2+ entry, and inhibition of thapsigargin-induced capacitative Ca2+ entry.

    PubMed

    Jan, C R; Ho, C M; Wu, S N; Tseng, C J

    1999-02-01

    The effect of 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF 96365) on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was examined. SKF 96365 at 25-100 microM evoked a robust [Ca2+]i transient in a dose-dependent manner, measured by fura-2 fluorimetry. A concentration of 10 microM SKF 96365 did not have an effect. The transient consisted of a slow rise, a gradual decay, and a sustained plateau in physiological Ca2+ medium. Removal of extracellular Ca2+ reduced the Ca2+ signals evoked by 50-100 microM SKF 96365 by nearly half in the area under the curve, suggesting that SKF 96365 induced intracellular Ca2+ release and also extracellular Ca2+ influx. A concentration of 100 microM SKF 96365 caused significant Mn2+ quench of fura-2 fluorescence, which was partly inhibited by La3+ (1 mM) or Gd3+ (0.1 mM), indicating that the SKF 96365-induced Ca2+ influx had two components: one is sensitive to La3+ (1 mM) or Gd3+ (0.1 mM), the other is not. The internal Ca2+ source for the SKF 96365-induced [Ca2+]i transient was the endoplasmic reticulum Ca2+ store because, pretreatment with thapsigargin and cyclopiazonic acid, two inhibitors of the endoplasmic reticulum Ca2+ pump nearly abolished the SKF 96365-induced [Ca2+]i increase in Ca2+-free medium. In contrast, pretreatment with 100 microM SKF 96365 only partly depleted the thapsigargin-sensitive Ca2+ store. Addition of 10 mM Ca2+ induced a significant [Ca2+]i increase after prior incubation with 100 microM SKF 96365 in Ca2+-free medium, demonstrating that SKF 96365 induced capacitative Ca2+ entry. This capacitative Ca2+ entry was about 40% of that induced by 1 microM thapsigargin. Additional to inducing its own capacitative Ca2+ entry, 100 microM SKF 96365 partly inhibited thapsigargin- or uridine trisphosphate (UTP)-induced capacitative Ca2+ entry. We also investigated the mechanisms underlying the decay of the SKF 96365-induced [Ca2+]i transient. Inhibition of the plasma

  18. A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

    PubMed

    Fernández, Silvina; Córdoba, Mariana

    2017-04-01

    Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC.

  19. Electrosynthesis of neodymium oxide nanorods and its nanocomposite with conjugated conductive polymer as a hybrid electrode material for highly capacitive pseudocapacitors.

    PubMed

    Mohammad Shiri, Hamid; Ehsani, Ali

    2017-06-01

    Herein, we report for the first time a facile and cost-efficient synthesis of metal oxide nanostructures comprised of nanorods type without the use of any additive. Nd(OH)3 and Nd2O3 nanorods were obtained by ultrasound wave assisted pulse electrochemical deposition in a Nd(NO3)3·6H2O nitrate bath. In addition, the interconnected nanorods were mesoporous leading to large electrochemical active sites for the redox reaction and fast ion transport within the Nd2O3 nanorods. Furthermore, for improving the electrochemical performance of conductive polymer, hybrid POAP/Nd2O3 films have then been fabricated by POAP electropolymerization in the presence of Nd2O3 nanorods as active electrodes for electrochemical supercapacitors. Surface and electrochemical analyses have been used for characterization of Nd2O3 and POAP/Nd2O3 composite films. Different electrochemical methods including galvanostatic charge discharge experiments, cyclic voltammetry and electrochemical impedance spectroscopy have been applied to study the system performance. Prepared composite film exhibited a significantly high specific capacity, high rate capability and excellent cycling stability. Importantly, electrochemical investigation show that POAP/Nd2O3 nanorods composite material has better properties than POAP without Nd2O3 nanorods, suggesting it can be used as supercapacitor electrode material with excellent specific capacitance (379Fg(-1)) which indicates this material is a promising electrode material for energy storage applications in high-performance pseudocapacitors.

  20. Determination of active doping in highly resistive boron doped silicon nanocrystals embedded in SiO2 by capacitance voltage measurement on inverted metal oxide semiconductor structure

    NASA Astrophysics Data System (ADS)

    Zhang, Tian; Puthen-Veettil, Binesh; Wu, Lingfeng; Jia, Xuguang; Lin, Ziyun; Yang, Terry Chien-Jen; Conibeer, Gavin; Perez-Wurfl, Ivan

    2015-10-01

    We investigate the Capacitance-Voltage (CV) measurement to study the electrically active boron doping in Si nanocrystals (ncSi) embedded in SiO2. The ncSi thin films with high resistivity (200-400 Ω cm) can be measured by using an inverted metal oxide semiconductor (MOS) structure (Al/ncSi (B)/SiO2/Si). This device structure eliminates the complications from the effects of lateral current flow and the high sheet resistance in standard lateral MOS structures. The characteristic MOS CV curves observed are consistent with the effective p-type doping. The CV modeling method is presented and used to evaluate the electrically active doping concentration. We find that the highly boron doped ncSi films have electrically active doping of 1018-1019 cm-3 despite their high resistivity. The saturation of doping at about 1.4 × 1019 cm-3 and the low doping efficiency less than 5% are observed and discussed. The calculated effective mobility is in the order of 10-3 cm2/V s, indicating strong impurity/defect scattering effect that hinders carriers transport.

  1. Determination of active doping in highly resistive boron doped silicon nanocrystals embedded in SiO{sub 2} by capacitance voltage measurement on inverted metal oxide semiconductor structure

    SciTech Connect

    Zhang, Tian Puthen-Veettil, Binesh; Wu, Lingfeng; Jia, Xuguang; Lin, Ziyun; Yang, Terry Chien-Jen; Conibeer, Gavin; Perez-Wurfl, Ivan

    2015-10-21

    We investigate the Capacitance-Voltage (CV) measurement to study the electrically active boron doping in Si nanocrystals (ncSi) embedded in SiO{sub 2}. The ncSi thin films with high resistivity (200–400 Ω cm) can be measured by using an inverted metal oxide semiconductor (MOS) structure (Al/ncSi (B)/SiO{sub 2}/Si). This device structure eliminates the complications from the effects of lateral current flow and the high sheet resistance in standard lateral MOS structures. The characteristic MOS CV curves observed are consistent with the effective p-type doping. The CV modeling method is presented and used to evaluate the electrically active doping concentration. We find that the highly boron doped ncSi films have electrically active doping of 10{sup 18}–10{sup 19 }cm{sup −3} despite their high resistivity. The saturation of doping at about 1.4 × 10{sup 19 }cm{sup −3} and the low doping efficiency less than 5% are observed and discussed. The calculated effective mobility is in the order of 10{sup −3} cm{sup 2}/V s, indicating strong impurity/defect scattering effect that hinders carriers transport.

  2. Nitric oxide released from activated platelets inhibits platelet recruitment.

    PubMed Central

    Freedman, J E; Loscalzo, J; Barnard, M R; Alpert, C; Keaney, J F; Michelson, A D

    1997-01-01

    Vessel injury and thrombus formation are the cause of most ischemic coronary syndromes and, in this setting, activated platelets stimulate platelet recruitment to the growing thrombus. Recently, a constitutive nitric oxide synthase (NOS) has been identified in human platelets. To further define the capacity of platelets to produce nitric oxide (NO), as well as to study the role of this NO in platelet recruitment, we adapted a NO-selective microelectrode for use in a standard platelet aggregometer, thereby permitting simultaneous measurement of platelet aggregation and NO production. Treatment of platelets with the NO synthase inhibitor -NG-nitroarginine methyl ester (L-NAME), reduced NO production by 92+/-8% in response to 5 microM ADP compared to control but increased aggregation by only 15+/-2%. In contrast, L-NAME had a more pronounced effect on platelet recruitment as evidenced by a 35+/-5% increase in the extent of aggregation, a 33+/-3% decrease in cyclic GMP content, and a 31+/-5% increase in serotonin release from a second recruitable population of platelets added to stimulated platelets at the peak of NO production. To study platelet recruitment accurately, we developed an assay that monitors two platelet populations simultaneously. Nonbiotinylated platelets were incubated with L-NAME or vehicle and activated with ADP. At peak NO production, biotinylated platelets were added. As measured by three-color flow cytometry, there was a 56+/-11% increase in the number of P selectin- positive platelets in the nonbiotinylated population treated with L-NAME as compared to control. When biotinylated platelets were added to the L-NAME-treated nonbiotinylated population, the number of P selectin positive biotinylated plate-lets increased by 180+/-32% as compared to biotinylated platelets added to the control. In summary, stimulated platelets produce NO that modestly inhibits platelet activation but markedly inhibits additional platelet recruitment. These data suggest

  3. Mechanisms of albuminuria in the chronic nitric oxide inhibition model.

    PubMed

    Arcos, M I; Fujihara, C K; Sesso, A; de Almeida Prado, E B; de Almeida Prado, M J; de Nucci, G; Zatz, R

    2000-12-01

    Chronic nitric oxide (NO) inhibition causes hypertension and renal injury. Concomitant salt overload promotes massive albuminuria. We investigated the mechanisms whereby these treatments impair glomerular permselectivity. Adult male Munich-Wistar rats received either a standard-salt (SS; 0.5% Na) or high-salt (HS; 3.1% Na) diet and either no treatment or the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). At 30 days, albuminuria was moderate, the density of fixed anionic sites at the glomerular basement membrane (GBM), estimated by cationic ferritin binding, declined by approximately 35%, and the fractional clearance of 70-kDa neutral dextran (phi) rose moderately in rats receiving L-NAME and SS. Rats given L-NAME and HS exhibited massive albuminuria, whereas phi was nearly tripled. Depletion of GBM anionic sites was also seen in these rats. The GBM was thickened in both L-NAME-treated groups. These abnormalities were largely reversed after cessation of treatments. These results indicate that chronic L-NAME treatment promotes reversible albuminuria by impairing both glomerular size and charge selectivity. These effects likely reflect functional rather than structural disruption of the glomerular wall.

  4. Inhibition of vitamin B12-dependent microbial growth by nitrous oxide

    SciTech Connect

    Alston, T.A. )

    1991-01-01

    In methionine-free media, nitrous oxide inhibits the growth of an auxotrophic strain of Escherichia coli lacking a cobalamin-independent pathway for the de novo synthesis of methionine. Prototrophic E. coli is similarly inhibited by nitrous oxide if the cobalamin-independent pathway is selectively depressed by sulfanilamide. Nitrous oxide thus effectively inactivates cobalamin-dependent 5-methyltetrahydrofolate-homocysteine methyltransferase in intact bacteria.

  5. Proteasome inhibition increases DNA and RNA oxidation in astrocyte and neuron cultures.

    PubMed

    Ding, Qunxing; Dimayuga, Edgardo; Markesbery, William R; Keller, Jeffrey N

    2004-12-01

    Increased levels of nucleic acid oxidation have been described as part of normal brain aging and have been demonstrated to occur in multiple neurological disorders. The basis for increased nucleic acid oxidation in each of these conditions is presently unknown. Proteasome inhibition occurs in a host of neurodegenerative conditions and likely contributes to increased levels of oxidative damage and neurotoxicity. In the present study we demonstrate for the first time the ability of proteasome inhibition to increase the level of nucleic acid oxidation in primary neuron and astrocyte cultures. Administration of proteasome inhibitors (MG262, MG115) at concentrations that do not induce neuron death in the first 24 h of treatment, dramatically increase the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8OHG) immunoreactivity in both cell types. Neurons underwent larger increases in nucleic acid oxidation compared to astrocyte cultures. While both DNA and RNA oxidation were observed following proteasome inhibition, RNA appeared to undergo a greater degree of oxidation than DNA. Both 18S and 28S ribosomal RNA were dramatically decreased following proteasome inhibition. Interestingly, an accumulation of unprocessed and/or cross-linked RNA species was observed following proteasome inhibition. Taken together, these data indicate the ability of proteasome inhibition to increase the levels of nucleic acid oxidation in both neurons and astrocytes, and suggest that proteasome inhibition may have deleterious effects on transcription and translation in both neurons and glia.

  6. Selective Inhibition of the Oxidation of Ferrous Iron or Sulfur in Thiobacillus ferrooxidans

    PubMed Central

    Harahuc, Lesia; Lizama, Hector M.; Suzuki, Isamu

    2000-01-01

    The oxidation of either ferrous iron or sulfur by Thiobacillus ferrooxidans was selectively inhibited or controlled by various anions, inhibitors, and osmotic pressure. Iron oxidation was more sensitive than sulfur oxidation to inhibition by chloride, phosphate, and nitrate at low concentrations (below 0.1 M) and also to inhibition by azide and cyanide. Sulfur oxidation was more sensitive than iron oxidation to the inhibitory effect of high osmotic pressure. These differences were evident not only between iron oxidation by iron-grown cells and sulfur oxidation by sulfur-grown cells but also between the iron and sulfur oxidation activities of the same iron-grown cells. Growth experiments with ferrous iron or sulfur as an oxidizable substrate confirmed the higher sensitivity of iron oxidation to inhibition by phosphate, chloride, azide, and cyanide. Sulfur oxidation was actually stimulated by 50 mM phosphate or chloride. Leaching of Fe and Zn from pyrite (FeS2) and sphalerite (ZnS) by T. ferrooxidans was differentially affected by phosphate and chloride, which inhibited the solubilization of Fe without significantly affecting the solubilization of Zn. PMID:10698768

  7. Red and white wines inhibit cholesterol oxidation induced by free radicals.

    PubMed

    Tian, Ling; Wang, Hua; Abdallah, Ahmed Moursy; Prinyawiwatkul, Witoon; Xu, Zhimin

    2011-06-22

    The capabilities of two red (RW) and two white wines (WW) in inhibiting cholesterol oxidation were evaluated using a cholesterol emulsion (CE) system. Each RW or WW was mixed with CE at different (v/v) ratios. Cholesterol oxidation was accelerated by a free radical generator, 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), at 37 °C. The major oxidation product, 7-ketocholesterol, was monitored to determine cholesterol stability in the CE system. At a ratio of 1:250 (RW/CE), 7-ketocholesterol production was not detected during 72 h of oxidation. At a 1:1000 ratio, the inhibition rate of each RW was maintained at 100% at 24 h but decreased afterward. Both WWs had 100% inhibition rate within 48 h at a ratio of 1:10. Also, the capabilities of catechin and resveratrol solutions (1 mg/mL) in inhibiting cholesterol oxidation were studied. Each of the wine polyphenolics showed a 100% of 7-ketocholesterol inhibition rate in 24 h at a ratio of 1:500 (solution/CE). However, the inhibition rate of resveratrol was lower than that of catechin at 48 or 72 h. The results demonstrated that red wine possesses great anti-cholesterol-oxidation capability, which may contribute to health benefits in preventing cardiovascular diseases. Catechin may play a more important role than resveratrol in inhibiting cholesterol oxidation.

  8. Inhibiting the photosensitized oxidation of anthracene and tryptophan by means of natural antioxidants

    NASA Astrophysics Data System (ADS)

    Aksenova, N. A.; Vyzhlova, E. N.; Malinovskaya, V. V.; Parfenov, V. V.; Solov'eva, A. B.; Timashev, P. S.

    2013-08-01

    It is shown that model reactions of photosensitized oxidation of anthracene and tryptophan can be used for evaluation and comparison of antioxidant activity of various classes of compounds. Inhibition of the oxidation of substrates in the presence of the familiar antioxidants tocopherol (vitamin E), ascorbic acid (vitamin C), and mixtures of these vitamins with methionine, and in the presence of reputed antioxidants dihydroquercetin and taurine, are considered. It is concluded that all of the above compounds except for taurine have antioxidant properties; i.e., they reduce the rate constants of the photosensitized oxidation of anthracene and tryptophan. It is found that the inhibition of oxidation is associated with the interaction between antioxidants and singlet oxygen. Analysis of the kinetic dependences of the photosensitized oxidation of substrates in the presence of antioxidants reveals that a mixture of vitamins inhibits the process most efficiently, and inhibition occurs at the initial stages due to more active interaction between singlet oxygen and vitamin C

  9. Origin and tunability of unusually large surface capacitance in doped cerium oxide studied by ambient-pressure X-ray photoelectron spectroscopy

    DOE PAGES

    Gopal, Chirranjeevi Balaji; Gabaly, Farid El; McDaniel, Anthony H.; ...

    2016-03-31

    Here, the volumetric redox (chemical) capacitance of the surface of CeO2–δ films is quantified in situ to be 100-fold larger than the bulk values under catalytically relevant conditions. Sm addition slightly lowers the surface oxygen nonstoichiometry, but effects a 10-fold enhancement in surface chemical capacitance by mitigating defect interactions, highlighting the importance of differential nonstoichiometry for catalysis.

  10. Origin and tunability of unusually large surface capacitance in doped cerium oxide studied by ambient-pressure X-ray photoelectron spectroscopy

    SciTech Connect

    Gopal, Chirranjeevi Balaji; Gabaly, Farid El; McDaniel, Anthony H.; Chueh, William C.

    2016-03-31

    Here, the volumetric redox (chemical) capacitance of the surface of CeO2–δ films is quantified in situ to be 100-fold larger than the bulk values under catalytically relevant conditions. Sm addition slightly lowers the surface oxygen nonstoichiometry, but effects a 10-fold enhancement in surface chemical capacitance by mitigating defect interactions, highlighting the importance of differential nonstoichiometry for catalysis.

  11. Inhibition of human low-density lipoprotein oxidation in vitro by ginger extracts.

    PubMed

    Gunathilake, K D Prasanna P; Rupasinghe, H P Vasantha

    2014-04-01

    Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in atherosclerotic plaque formation. Currently, there is a renewed interest in ginger because of its antioxidants and cardioprotective properties. The effects of ethanol, methanol, ethyl acetate, and hexane solvent extracts of ginger and pure major ginger constituents on Cu(2+)-induced oxidation of human LDL in vitro were examined. The LDL oxidation inhibition by ethanol, methanol, ethyl acetate, and hexane extracts of ginger was 71%, 76%, 67%, and 67%, respectively, at their optimum extraction conditions. Inhibition of LDL oxidation by water extracts of ginger, which was prepared by ultrasonic-assisted extraction conditions of 52°C for 15 min, was about 43%. Phenolic bioactives of ginger-6-gingerols, 8-gingerols, 10-gingerols, and 6-shogaol-seem to be strong inhibitors of Cu(+2)-induced LDL oxidation. Overall, ginger extracts, including the water extract possess the antioxidant activities to inhibit human LDL oxidation in vitro.

  12. Capacitive Power Transfer

    DTIC Science & Technology

    2010-12-15

    capacitive charger achieves near 80% e ciency at 3.7W with only 63 pF of coupling capacitance. An automatic tuning loop adjusts the frequency from...find the optimum circuit component values and operating point. A prototype capacitive charger achieves near 80% efficiency at 3.7 W with only 63 pF of...delivery in a smartphone sized package . Section 5 presents work in progress on a capacitively isolated LED driver. 2 Analysis The analysis is based on a

  13. Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells

    NASA Technical Reports Server (NTRS)

    Koh, T. J.; Tidball, J. G.

    2000-01-01

    We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide donor sodium nitroprusside prevented many of the effects of calcium ionophore on C(2)C(12) muscle cells, including preventing talin proteolysis and release into the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular protein. These results indicate that nitric oxide inhibition of calpain protected the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell-permeable calpastatin peptide also protected the cells from proteolysis, confirming that ionophore-induced proteolysis was primarily calpain mediated. The activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside, and this inhibition was reversed by dithiothreitol. Previous incubation with the active site-targeted calpain inhibitor I prevented most of the sodium nitroprusside-induced inhibition of m-calpain activity. These data suggest that nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site cysteine. The results of this study indicate that nitric oxide produced endogenously by skeletal muscle and other cell types has the potential to inhibit m-calpain activity and cytoskeletal proteolysis.

  14. The production of nitric oxide by marine ammonia-oxidizing archaea and inhibition of archaeal ammonia oxidation by a nitric oxide scavenger.

    PubMed

    Martens-Habbena, Willm; Qin, Wei; Horak, Rachel E A; Urakawa, Hidetoshi; Schauer, Andrew J; Moffett, James W; Armbrust, E Virginia; Ingalls, Anitra E; Devol, Allan H; Stahl, David A

    2015-07-01

    Nitrification is a critical process for the balance of reduced and oxidized nitrogen pools in nature, linking mineralization to the nitrogen loss processes of denitrification and anammox. Recent studies indicate a significant contribution of ammonia-oxidizing archaea (AOA) to nitrification. However, quantification of the relative contributions of AOA and ammonia-oxidizing bacteria (AOB) to in situ ammonia oxidation remains challenging. We show here the production of nitric oxide (NO) by Nitrosopumilus maritimus SCM1. Activity of SCM1 was always associated with the release of NO with quasi-steady state concentrations between 0.05 and 0.08 μM. NO production and metabolic activity were inhibited by the nitrogen free radical scavenger 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). Comparison of marine and terrestrial AOB strains with SCM1 and the recently isolated marine AOA strain HCA1 demonstrated a differential sensitivity of AOB and AOA to PTIO and allylthiourea (ATU). Similar to the investigated AOA strains, bulk water column nitrification at coastal and open ocean sites with sub-micromolar ammonia/ammonium concentrations was inhibited by PTIO and insensitive to ATU. These experiments support predictions from kinetic, molecular and biogeochemical studies, indicating that marine nitrification at low ammonia/ammonium concentrations is largely driven by archaea and suggest an important role of NO in the archaeal metabolism.

  15. Intensification of chemiluminescence in the inhibited oxidation of oils

    SciTech Connect

    Nikolayevskii, A.N.; Filippenko, T.A.; Sergovskaya, T.S.

    1982-01-01

    Chemiluminescence is intensified upon the addition of inhibitors (phloroglucinol, p-phenylenediamine, hydroquinone) to oxidized sunflower oil. The formation of a further source of chemiluminescence is explained by reactions of the oxidized oil and the inhibitors. Oxidation initiated by azoisobutyronitrile of sunflower oil using atmospheric oxygen was performed at 70/sup 0/C in chlorobenzene solution; 9,10-dibromoanthracene was the luminescence activator. 4 figures.

  16. Capacitive electrodes in electroencephalography.

    PubMed

    von Ellenrieder, Nicolás; Spinelli, Enrique; Muravchik, Carlos H

    2006-01-01

    We present a forward problem formulation for computing biopotentials measured with dry or capacitive electrodes. This formulation is not quasistatic and has mixed boundary conditions. Our results show that simple approximations to the measurements based on capacitive coupling are adequate in most situations. We study the range of validity and errors committed in the EEG forward and inverse problems when using this approximation.

  17. Hibiscus anthocyanins-rich extract inhibited LDL oxidation and oxLDL-mediated macrophages apoptosis.

    PubMed

    Chang, Yun-Ching; Huang, Kai-Xun; Huang, An-Chung; Ho, Yung-Chyuan; Wang, Chau-Jong

    2006-07-01

    The oxidative modification of low-density lipoprotein (LDL) plays a key role in the pathogenesis of atherosclerosis. Anti-oxidative reagents, which can effectively inhibit LDL oxidation, may prevent atherosclerosis via reducing early atherogenesis, and slowing down the progression to advance stages. As shown in previous studies Hibiscus sabdariffa L. is a natural plant containing a lot of pigments that was found to possess anti-oxidative of activity. Therefore, in this study, we evaluated the anti-oxidative activity of Hibiscus anthocyanins (HAs) by measuring their effects on LDL oxidation (in cell-free system) and anti-apoptotic abilities (in RAW264.7 cells). HAs have been tested in vitro examining their relative electrophoretic mobility (REM), Apo B fragmentation, thiobarbituric acid relative substances (TBARS) and radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay. The anti-oxidative activity of HAs was defined by relative electrophoretic mobility of oxLDL (decrease of 50% at 2 mg/ml), fragmentation of Apo B (inhibition of 61% at 1mg/ml), and TBARS assay (IC(50): 0.46 mg/ml) in the Cu(2+)-mediated oxidize LDL. Furthermore, the addition of >0.1 mg/ml of HAs could scavenge over 95% of free DPPH radicals, HAs showed strong potential in inhibiting LDL oxidation induced by copper. In addition, to determine whether oxLDL-induced apoptosis in macrophages is inhibited by HAs, we studied the viability, morphology and caspase-3 expression of RAW 264.7 cells. MTT assay, Leukostate staining analysis and Western blotting reveals that HAs could inhibit oxLDL-induced apoptosis. According to these findings, we suggest that HAs may be used to inhibit LDL oxidation and oxLDL-mediated macrophage apoptosis, serving as a chemopreventive agent. However, further investigations into the specificity and mechanism(s) of HAs are needed.

  18. Inhibition of a protein tyrosine phosphatase using mesoporous oxides.

    PubMed

    Kapoor, S; Girish, T S; Mandal, S S; Gopal, B; Bhattacharyya, A J

    2010-03-11

    The feasibility of utilizing mesoporous matrices of alumina and silica for the inhibition of enzymatic activity is presented here. These studies were performed on a protein tyrosine phosphatase by the name chick retinal tyrosine phosphotase-2 (CRYP-2), a protein that is identical in sequence to the human glomerular epithelial protein-1 and involved in hepatic carcinoma. The inhibition of CRYP-2 is of tremendous therapeutic importance. Inhibition of catalytic activity was examined using the sustained delivery of p-nitrocatechol sulfate (pNCS) from bare and amine functionalized mesoporous silica (MCM-48) and mesoporous alumina (Al(2)O(3)). Among the various mesoporous matrices employed, amine functionalized MCM-48 exhibited the best release of pNCS and also inhibition of CRYP-2. The maximum speed of reaction v(max) (=160 +/- 10 micromol/mnt/mg) and inhibition constant K(i) (=85.0 +/- 5.0 micromol) estimated using a competitive inhibition model were found to be very similar to inhibition activities of protein tyrosine phosphatases using other methods.

  19. Inhibition of palm oil oxidation by zeolite nanocrystals.

    PubMed

    Tan, Kok-Hou; Awala, Hussein; Mukti, Rino R; Wong, Ka-Lun; Rigaud, Baptiste; Ling, Tau Chuan; Aleksandrov, Hristiyan A; Koleva, Iskra Z; Vayssilov, Georgi N; Mintova, Svetlana; Ng, Eng-Poh

    2015-05-13

    The efficiency of zeolite X nanocrystals (FAU-type framework structure) containing different extra-framework cations (Li(+), Na(+), K(+), and Ca(2+)) in slowing the thermal oxidation of palm oil is reported. The oxidation study of palm oil is conducted in the presence of zeolite nanocrystals (0.5 wt %) at 150 °C. Several characterization techniques such as visual analysis, colorimetry, rheometry, total acid number (TAN), FT-IR spectroscopy, (1)H NMR spectroscopy, and Karl Fischer analyses are applied to follow the oxidative evolution of the oil. It was found that zeolite nanocrystals decelerate the oxidation of palm oil through stabilization of hydroperoxides, which are the primary oxidation product, and concurrently via adsorption of the secondary oxidation products (alcohols, aldehydes, ketones, carboxylic acids, and esters). In addition to the experimental results, periodic density functional theory (DFT) calculations are performed to elucidate further the oxidation process of the palm oil in the presence of zeolite nanocrystals. The DFT calculations show that the metal complexes formed with peroxides are more stable than the complexes with alkenes with the same ions. The peroxides captured in the zeolite X nanocrystals consequently decelerate further oxidation toward formation of acids. Unlike the monovalent alkali metal cations in the zeolite X nanocrystals (K(+), Na(+), and Li(+)), Ca(2+) reduced the acidity of the oil by neutralizing the acidic carboxylate compounds to COO(-)(Ca(2+))1/2 species.

  20. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage.

    PubMed

    Gokay, Nevzat Selim; Yilmaz, Ibrahim; Komur, Baran; Demiroz, Ahu Senem; Gokce, Alper; Dervisoglu, Sergülen; Gokay, Banu Vural

    2016-01-01

    The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg), inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg), or nitric oxide precursor L-arginine (200 mg/kg). After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P = 0.044) positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

  1. A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

    PubMed Central

    Gokay, Nevzat Selim; Yilmaz, Ibrahim; Demiroz, Ahu Senem; Gokce, Alper; Dervisoglu, Sergülen; Gokay, Banu Vural

    2016-01-01

    The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg), inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg), or nitric oxide precursor L-arginine (200 mg/kg). After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P = 0.044) positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders. PMID:27382570

  2. Capacitance measuring device

    DOEpatents

    Andrews, W.H. Jr.

    1984-08-01

    A capacitance measuring circuit is provided in which an unknown capacitance is measured by comparing the charge stored in the unknown capacitor with that stored in a known capacitance. Equal and opposite voltages are repetitively simultaneously switched onto the capacitors through an electronic switch driven by a pulse generator to charge the capacitors during the ''on'' portion of the cycle. The stored charge is compared by summing discharge currents flowing through matched resistors at the input of a current sensor during the ''off'' portion of the switching cycle. The net current measured is thus proportional to the difference in value of the two capacitances. The circuit is capable of providing much needed accuracy and stability to a great variety of capacitance-based measurement devices at a relatively low cost.

  3. Ferrous iron oxidation by Thiobacillus ferrooxidans: inhibition with benzoic acid, sorbic acid and sodium lauryl sulfate

    SciTech Connect

    Onysko, S.J.

    1984-07-01

    Acid mine drainage is formed by the weathering or oxidation of pyritic material exposed during coal mining. The rate of pyritic material oxidation can be greatly accelerated by certain acidophilic bacteria such as Thiobacillus ferrooxidans which catalyse the oxidation of ferrous to ferric iron. A number of organic compounds, under laboratory conditions, can apparently inhibit both the oxidation of ferrous to ferric iron by T. ferrooxidans and the weathering of pyritic material by mixed cultures of acid mine drainage micro-organisms. Sodium lauryl sulphate (SLS), an anionic surfactant has proved effective in this respect. Benzoic acid, sorbic acid and SLS at low concentrations, each effectively inhibited bacterial oxidation of ferrous iron in batch cultures of T. ferrooxidans. The rate of chemical oxidation of ferrous iron in low pH, sterile, batch reactors was not substantially affected at the tested concentrations of any of the compounds.

  4. Pimaradienoic Acid Inhibits Carrageenan-Induced Inflammatory Leukocyte Recruitment and Edema in Mice: Inhibition of Oxidative Stress, Nitric Oxide and Cytokine Production

    PubMed Central

    Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation. PMID:26895409

  5. Proliferation of macrophages due to the inhibition of inducible nitric oxide synthesis by oxidized low-density lipoproteins

    PubMed Central

    Brunner, Monika; Gruber, Miriam; Schmid, Diethart; Baran, Halina; Moeslinger, Thomas

    2015-01-01

    Oxidized low-density lipoprotein (ox-LDL) is assumed to be a major causal agent in hypercholesteraemia-induced atherosclerosis. Because the proliferation of lipid-loaden macrophages within atherosclerotic lesions has been described, we investigated the dependence of macrophage proliferation on the inhibition of inducible nitric oxide synthase (iNOS) by hypochlorite oxidized LDL. Ox-LDL induces a dose dependent inhibition of inducible nitric oxide synthesis in lipopolysaccharide-interferon stimulated mouse macrophages (J774.A1) with concomitant macrophage proliferation as assayed by cell counting, tritiated-thymidine incorporation and measurement of cell protein. Native LDL did not influence macrophage proliferation and inducible nitric oxide synthesis. iNOS protein and mRNA was reduced by HOCl-oxidized LDL (0-40 µg/ml) as revealed by immunoblotting and competitive semiquantitative PCR. Macrophage proliferation was increased by the addition of the iNOS inhibitor L-NAME. The addition of ox-LDL to L-NAME containing incubations induced no further statistically significant increase in cell number. Nitric oxide donors decreased ox-LDL induced macrophage proliferation and nitric oxide scavengers restored macrophage proliferation to the initial values achieved by ox-LDL. The decrease of cytosolic DNA fragments in stimulated macrophages incubated with ox-LDL demonstrates that the proliferative actions of ox-LDL are associated with a decrease of NO-induced apoptosis. Our data show that inhibition of iNOS dependent nitric oxide production caused by hypochlorite oxidized LDL enhances macrophage proliferation. This might be a key event in the pathogenesis of atherosclerotic lesions. PMID:26600745

  6. Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans

    PubMed Central

    Pialoux, Vincent; Poulin, Marc J.; Hemmelgarn, Brenda R.; Muruve, Daniel A.; Chirico, Erica N.; Faes, Camille; Sola, Darlene Y.; Ahmed, Sofia B.

    2017-01-01

    Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (−20%). Cycloxygenase-2 inhibition significantly limited the increase in 8-hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug. PMID:28344559

  7. Functionalization of Titanium Alloy Surface by Graphene Nanoplatelets and Metal Oxides: Corrosion Inhibition.

    PubMed

    Mondal, Jayanta; Aarik, Lauri; Kozlova, Jekaterina; Niilisk, Ahti; Mändar, Hugo; Mäeorg, Uno; Simões, Alda; Sammelselg, Väino

    2015-09-01

    Corrosion inhibition of metallic substrates is an important and crucial step for great economical as well as environmental savings. In this paper, we introduce an extra thin effective corrosion inhibitive material having layered structure designed for protection and functionalization of Ti Grade 5 alloy substrates. The coating consists of a first layer made of thin graphene nanoplatelets, on top of which a multilayer Al2O3 and TiO2 films is applied by low-temperature atomic layer deposition. The amorphous structure of the metal oxide films was confirmed by micro-Raman and X-ray diffraction analysis. Corrosion inhibition ability of the prepared coatings was analyzed by open circuit potential, potentiodynamic plot and by voltammetric analysis, in aqueous potassium bromide solution. The open circuit potential of the graphene-metal oxide coated substrate showed much passive nature than bare substrate or graphene coated or only metal oxide coated substrates. The localized corrosion potential of the graphene-metal oxide coated, only metal oxide coated, and bare substrates were found 5.5, 3.0, and 1.1 V, respectively. In addition, corrosion current density values of the graphene-metal oxide and only metal oxide coated substrates showed much more passive nature than the bare and graphene coated substrates. Long immersion test in the salt solution further clarified the effective corrosion inhibition of the graphene-metal oxide coated substrate. The analyzed results reflect that the graphene-metal oxide films can be used to prepare better and effective corrosion inhibition coatings for the Ti Grade 5 alloy to increase their lifetime.

  8. Tamoxifen inhibits mitochondrial oxidative stress damage induced by copper orthophenanthroline.

    PubMed

    Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Correa, Francisco; Díaz-Ruiz, Jorge Luis; Chávez, Edmundo

    2016-12-01

    In this work, we studied the effect of tamoxifen and cyclosporin A on mitochondrial permeability transition caused by addition of the thiol-oxidizing pair Cu(2+) -orthophenanthroline. The findings indicate that tamoxifen and cyclosporin A circumvent the oxidative membrane damage manifested by matrix Ca(2+) release, mitochondrial swelling, and transmembrane electrical gradient collapse. Furthermore, it was found that tamoxifen and cyclosporin A prevent the generation of TBARs promoted by Cu(2+) -orthophenanthroline, as well as the inactivation of the mitochondrial enzyme aconitase and disruption of mDNA. Electrophoretic analysis was unable to demonstrate a cross-linking reaction between membrane proteins. Yet, it was found that Cu(2+) -orthophenanthroline induced the generation of reactive oxygen species. It is thus plausible that membrane leakiness is due to an oxidative stress injury.

  9. Capacitance pressure sensor

    DOEpatents

    Eaton, William P.; Staple, Bevan D.; Smith, James H.

    2000-01-01

    A microelectromechanical (MEM) capacitance pressure sensor integrated with electronic circuitry on a common substrate and a method for forming such a device are disclosed. The MEM capacitance pressure sensor includes a capacitance pressure sensor formed at least partially in a cavity etched below the surface of a silicon substrate and adjacent circuitry (CMOS, BiCMOS, or bipolar circuitry) formed on the substrate. By forming the capacitance pressure sensor in the cavity, the substrate can be planarized (e.g. by chemical-mechanical polishing) so that a standard set of integrated circuit processing steps can be used to form the electronic circuitry (e.g. using an aluminum or aluminum-alloy interconnect metallization).

  10. Capacitive chemical sensor

    DOEpatents

    Manginell, Ronald P; Moorman, Matthew W; Wheeler, David R

    2014-05-27

    A microfabricated capacitive chemical sensor can be used as an autonomous chemical sensor or as an analyte-sensitive chemical preconcentrator in a larger microanalytical system. The capacitive chemical sensor detects changes in sensing film dielectric properties, such as the dielectric constant, conductivity, or dimensionality. These changes result from the interaction of a target analyte with the sensing film. This capability provides a low-power, self-heating chemical sensor suitable for remote and unattended sensing applications. The capacitive chemical sensor also enables a smart, analyte-sensitive chemical preconcentrator. After sorption of the sample by the sensing film, the film can be rapidly heated to release the sample for further analysis. Therefore, the capacitive chemical sensor can optimize the sample collection time prior to release to enable the rapid and accurate analysis of analytes by a microanalytical system.

  11. Nitric oxide inhibition sustains vasopressin-induced vasoconstriction.

    PubMed Central

    Dworkin, M. J.; Carnochan, P.; Allen-Mersh, T. G.

    1995-01-01

    Hepatic parenchymal vasoconstriction increases cytotoxic drug uptake into hepatic metastases by increasing the tumour to liver blood flow ratio. Prolonged infusion of the vasoconstrictor vasopressin does not result in sustained vasoconstriction, and this may limit the benefit of vasopressin in infusional chemotherapy. We have assessed whether loss of vasopressin-induced vasoconstriction is mediated by nitric oxide. Hepatic and tumour blood flow were continuously monitored, in an animal hepatic tumour model, by laser Doppler flowmetry. The response to regionally infused vasopressin and the nitric oxide inhibitor N-nitro-L-arginine methyl ester (L-NAME) were assessed over a 30 min infusion period. The vasopressin-induced vasoconstrictor effect diminished after 15 min despite continued infusion. Vasoconstriction was significantly prolonged when L-NAME was infused in addition to vasopressin. The increase in tumour to normal blood flow ratio was greater over the infusion period when L-NAME was co-administered with vasopressin. Our results suggest that the loss of vasopressin-induced vasoconstriction seen in liver parenchyma after regional infusion is prevented by the nitric oxide synthase inhibitor L-name and may be mediated by nitric oxide. PMID:7734317

  12. Inhibition of methane oxidation by Methylococcus capsulatus with hydrochlorofluorocarbons and fluorinated methanes

    USGS Publications Warehouse

    Matheson, L.J.; Jahnke, L.L.; Oremland, R.S.

    1997-01-01

    The inhibition of methane oxidation by cell suspensions of Methylococcus capsulatus (Bath) exposed to hydrochlorofluorocarbon 21 (HCFC-21; difluorochloromethane [CHF2Cl]), HCFC-22 (fluorodichloromethane [CHFCl2]), and various fluorinated methanes was investigated. HCFC-21 inhibited methane oxidation to a greater extent than HCFC-22, for both the particulate and soluble methane monooxygenases. Among the fluorinated methanes, both methyl fluoride (CH3F) and difluoromethane (CH2F2) were inhibitory while fluoroform (CHF3) and carbon tetrafluoride (CF4) were not. The inhibition of methane oxidation by HCFC-21 and HCFC-22 was irreversible, while that by methyl fluoride was reversible. The HCFCs also proved inhibitory to methanol dehydrogenase, which suggests that they disrupt other aspects of C1 catabolism in addition to methane monooxygenase activity.

  13. Nitric oxide inhibits the formation of zinc protoporphyrin IX and protoporphyrin IX.

    PubMed

    Wakamatsu, Jun-ichi; Hayashi, Nobutaka; Nishimura, Takanori; Hattori, Akihito

    2010-01-01

    The aim of this study was to elucidate the mechanism by which curing agents, especially nitrite, inhibit the formation of zinc protoporphyrin IX (ZPP) in dry-cured hams such as Parma ham. The oxidation-reduction potential of model solutions was increased by the addition of nitrite, but it was not clear whether the formation of ZPP is inhibited by the oxidizing property of nitrite. The effect of nitric oxide (NO) produced from nitrite on the formation of ZPP was examined. The amount of ZPP formed was decreased by the addition of NO donors. The amount of protoporphyrin IX (PPIX), which is the precursor of ZPP, was also decreased by the addition of NO donors. It is concluded that NO produced from nitrite inhibited the formation of PPIX and ZPP was therefore not formed in cured meat products with the addition of nitrite or nitrate.

  14. Impact of GaN cap on charges in Al₂O₃/(GaN/)AlGaN/GaN metal-oxide-semiconductor heterostructures analyzed by means of capacitance measurements and simulations

    SciTech Connect

    Ťapajna, M. Jurkovič, M.; Válik, L.; Haščík, Š.; Gregušová, D.; Kuzmík, J.; Brunner, F.; Cho, E.-M.; Hashizume, T.

    2014-09-14

    Oxide/semiconductor interface trap density (D{sub it}) and net charge of Al₂O₃/(GaN)/AlGaN/GaN metal-oxide-semiconductor high-electron mobility transistor (MOS-HEMT) structures with and without GaN cap were comparatively analyzed using comprehensive capacitance measurements and simulations. D{sub it} distribution was determined in full band gap of the barrier using combination of three complementary capacitance techniques. A remarkably higher D{sub it} (∼5–8 × 10¹²eV⁻¹ cm⁻²) was found at trap energies ranging from EC-0.5 to 1 eV for structure with GaN cap compared to that (D{sub it} ∼ 2–3 × 10¹²eV⁻¹ cm⁻²) where the GaN cap was selectively etched away. D{sub it} distributions were then used for simulation of capacitance-voltage characteristics. A good agreement between experimental and simulated capacitance-voltage characteristics affected by interface traps suggests (i) that very high D{sub it} (>10¹³eV⁻¹ cm⁻²) close to the barrier conduction band edge hampers accumulation of free electron in the barrier layer and (ii) the higher D{sub it} centered about EC-0.6 eV can solely account for the increased C-V hysteresis observed for MOS-HEMT structure with GaN cap. Analysis of the threshold voltage dependence on Al₂O₃ thickness for both MOS-HEMT structures suggests that (i) positive charge, which compensates the surface polarization, is not necessarily formed during the growth of III-N heterostructure, and (ii) its density is similar to the total surface polarization charge of the GaN/AlGaN barrier, rather than surface polarization of the top GaN layer only. Some constraints for the positive surface compensating charge are discussed.

  15. The 5-Lipoxygenase Inhibitor Zileuton Confers Neuroprotection against Glutamate Oxidative Damage by Inhibiting Ferroptosis.

    PubMed

    Liu, Yang; Wang, Wei; Li, Yuyao; Xiao, Yunqi; Cheng, Jian; Jia, Jia

    2015-01-01

    5-Lipoxygenase (5-LOX) inhibitors have been shown to be protective in several neurodegenerative disease models; however, the underlying mechanisms remain unclear. We investigated whether 5-LOX inhibitor zileuton conferred direct neuroprotection against glutamate oxidative toxicity by inhibiting ferroptosis, a newly identified iron-dependent programmed cell death. Treatment of HT22 mouse neuronal cell line with glutamate resulted in significant cell death, which was inhibited by zileuton in a dose-dependent manner. Consistently, zileuton decreased glutamate-induced production of reactive oxygen species but did not restore glutamate-induced depletion of glutathione. Moreover, the pan-caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (ZVAD-fmk) neither prevented HT22 cell death induced by glutamate nor affected zileuton protection against glutamate oxidative toxicity, suggesting that zileuton did not confer neuroprotection by inhibiting caspase-dependent apoptosis. Interestingly, glutamate-induced HT22 cell death was significantly inhibited by the ferroptosis inhibitor ferrostatin-1. Moreover, zileuton protected HT22 neuronal cells from erastin-induced ferroptosis. However, we did not observe synergic protective effects of zileuton and ferrostatin-1 on glutamate-induced cell death. These results suggested that both the 5-LOX inhibitor zileuton and the ferropotosis inhibitor ferrostatin-1 acted through the same cascade to protect against glutamate oxidative toxicity. In conclusion, our results suggested that zileuton protected neurons from glutamate-induced oxidative stress at least in part by inhibiting ferroptosis.

  16. Nitric oxide synthases activation and inhibition by metallacarborane-cluster-based isoform-specific affectors.

    PubMed

    Kaplánek, Robert; Martásek, Pavel; Grüner, Bohumír; Panda, Satya; Rak, Jakub; Masters, Bettie Sue Siler; Král, Vladimír; Roman, Linda J

    2012-11-26

    A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic boron cluster system, previously used for boron neutron capture therapy, was modified by the addition of positively charged moieties to its periphery, providing hydrophobic and nonclassical hydrogen bonding interactions with the protein. Several of these compounds show efficacy for inhibition of NO synthesis with differential effects on the various nitric oxide synthase isoforms.

  17. Antioxidant and nitric oxide inhibition activities of Thai medicinal plants.

    PubMed

    Makchuchit, Sunita; Itharat, Arunporn; Tewtrakul, Supinya

    2010-12-01

    Nineteen Thai medicinal plants used in Thai traditional medicine preparation to treat colds, asthma and fever were studied for their antioxidant and NO inhibitory activities. Three extracts were obtained from each plant. First extract obtained by macerating the plant part in 95% ethanol (Et) residue was boiled in water, where water extract (EW) was obtained. The third extract (HW) was obtained by boiling each plant in water similar to that of Thai traditional medicine practice. These extracts were tested for their antioxidant activity using DPPH assay, and anti-inflammatory activity by determination of inhibitory activity on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines using Griess reagent. Results indicated that Et, EW and HW of Syzygium aromaticum showed the highest antioxidant activity (EC50 = 6.56, 4.73 and 5.30 microg/ml, respectively). Et of Atractylodes lancea exhibited the most potent inhibitory activity on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cells, with IC50 value of 9.70 microg/ml, followed by Et of Angelica sinensis and Cuminum cyminum (IC50 = 12.52 and 13.56 microg/ml, respectively) but water extract (EW, HW) of all plants were apparently inactive. These results of anti-inflammatory activity of these plants correspond with the traditional use for fever; cold, allergic-related diseases and inflammatory-related diseases.

  18. Isolated tumoral pyruvate dehydrogenase can synthesize acetoin which inhibits pyruvate oxidation as well as other aldehydes.

    PubMed

    Baggetto, L G; Lehninger, A L

    1987-05-29

    Oxidation of 1 mM pyruvate by Ehrlich and AS30-D tumor mitochondria is inhibited by acetoin, an unusual and important metabolite of pyruvate utilization by cancer cells, by acetaldehyde, methylglyoxal and excess pyruvate. The respiratory inhibition is reversed by other substrates added to pyruvate and also by 0.5 mM ATP. Kinetic properties of pyruvate dehydrogenase complex isolated from these tumor mitochondria have been studied. This complex appears to be able to synthesize acetoin from acetaldehyde plus pyruvate and is competitively inhibited by acetoin. The role of a new regulatory pattern for tumoral pyruvate dehydrogenase is presented.

  19. Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

    PubMed Central

    Wang, Ye; Yang, Qi-Wei; Yang, Qing; Zhou, Tie; Shi, Min-Feng; Sun, Chen-Xia; Gao, Xiu-Xia; Cheng, Yan-Qiong; Cui, Xin-Gang; Sun, Ying-Hao

    2017-01-01

    Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy.

  20. Kinetic Constants for Biological Ammonium and Nitrite Oxidation Processes Under Sulfide Inhibition.

    PubMed

    Bejarano-Ortiz, Diego Iván; Huerta-Ochoa, Sergio; Thalasso, Frédéric; Cuervo-López, Flor de María; Texier, Anne-Claire

    2015-12-01

    Inhibition of nitrification by sulfide was assessed using sludge obtained from a steady-state nitrifying reactor. Independent batch activity assays were performed with ammonium and nitrite as substrate, in order to discriminate the effect of sulfide on ammonium and nitrite oxidation. In the absence of sulfide, substrate affinity constants (K S,NH4  = 2.41 ± 0.11 mg N/L; K s, NO2  = 0.74 ± 0.03 mg N/L) and maximum specific rates (q max,NH4  = 0.086 ± 0.008 mg N/mg microbial protein h; q max,NO2  = 0.124 ± 0.001 mg N/mg microbial protein h) were determined. Inhibition of ammonium oxidation was no-competitive (inhibition constant (K i , NH4 ) of 2.54 ± 0.12 mg HS(-)-S/L) while inhibition of nitrite oxidation was mixed (competitive inhibition constant (K' i , NO2 ) of 0.22 ± 0.03 mg HS(-)-S/L and no-competitive inhibition constant (K i , NO2 ) of 1.03 ± 0.06 mg HS(-)-S/L). Sulfide has greater inhibitory effect on nitrite oxidation than ammonium oxidation, and its presence in nitrification systems should be avoided to prevent accumulation of nitrite. By simulating the effect of sulfide addition in a continuous nitrifying reactor under steady-state operation, it was shown that the maximum sulfide concentration that the sludge can tolerate without affecting the ammonium consumption efficiency and nitrate yield is 1 mg HS(-)-S/L.

  1. Glyphosate Inhibits PPAR Gamma Induction and Differentiation of Preadipocytes and is able to Induce Oxidative Stress.

    PubMed

    Martini, Claudia N; Gabrielli, Matías; Brandani, Javier N; Vila, María Del C

    2016-08-01

    Glyphosate-based herbicides (GF) are extensively used for weed control. Thus, it is important to investigate their putative toxic effects. We have reported that GF at subagriculture concentrations inhibits proliferation and differentiation to adipocytes of 3T3-L1 fibroblasts. In this investigation, we evaluated the effect of GF on genes upregulated during adipogenesis. GF was able to inhibit the induction of PPAR gamma, the master gene in adipogenesis but not C/EBP beta, which precedes PPAR gamma activation. GF also inhibited differentiation and proliferation of another model of preadipocyte: mouse embryonic fibroblasts. In exponentially growing 3T3-L1 cells, GF increased lipid peroxidation and the activity of the antioxidant enzyme, superoxide dismutase. We also found that proliferation was inhibited with lower concentrations of GF when time of exposure was extended. Thus, GF was able to inhibit proliferation and differentiation of preadipocytes and to induce oxidative stress, which is indicative of its ability to alter cellular physiology.

  2. Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL.

    PubMed

    Ishikawa, K; Navab, M; Leitinger, N; Fogelman, A M; Lusis, A J

    1997-09-01

    Heme catabolic processes produce the antioxidants biliverdin and bilirubin, as well as the potent prooxidant free iron. Since these products have opposing effects on oxidative stress, it is not clear whether heme catabolism promotes or inhibits inflammatory processes, including atherosclerotic lesion formation. Heme oxygenase (HO) catalyzes the rate-limiting step of heme catabolism. We used cocultures of human aortic endothelial cells and smooth muscle cells to examine the possible role of HO in early atherosclerosis. Heme oxygenase-1 (HO-1), the inducible isoform of HO, was highly induced by mildly oxidized LDL, and augmented induction was observed with hemin pretreatment. This augmented HO-1 induction resulted in the reduction of monocyte chemotaxis in response to LDL oxidation. Conversely, inhibition of HO by a specific inhibitor, Sn-protoporphyrin IX, enhanced chemotaxis. Furthermore, pretreatment with biliverdin or bilirubin, the products of HO, reduced chemotaxis. Oxidized phospholipids in the mildly oxidized LDL appear to be responsible for HO-1 induction, since oxidized but not native arachidonic acid-containing phospholipids also induced HO-1. These results suggest that HO-1 induced by mildly oxidized LDL may protect against the induction of inflammatory responses in artery wall cells through the production of the antioxidants biliverdin and bilirubin.

  3. Coumestan inhibits radical-induced oxidation of DNA: is hydroxyl a necessary functional group?

    PubMed

    Xi, Gao-Lei; Liu, Zai-Qun

    2014-06-18

    Coumestan is a natural tetracycle with a C═C bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(•+)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by (•)OH, Cu(2+)/glutathione (GSH), and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit (•)OH-, Cu(2+)/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit (•)OH- and Cu(2+)/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant.

  4. Atorvastatin protects cardiomyocytes from oxidative stress by inhibiting LOX-1 expression and cardiomyocyte apoptosis.

    PubMed

    Zhang, Lei; Cheng, Linfang; Wang, Qiqi; Zhou, Dongchen; Wu, Zhigang; Shen, Ling; Zhang, Li; Zhu, Jianhua

    2015-03-01

    Coronary artery disease (CAD) is a major health problem worldwide. The most severe form of CAD is acute coronary syndrome (ACS). Recent studies have demonstrated the beneficial role of atorvastatin in ACS; however, the mechanisms underlying this effect have not been fully clarified. Growing evidence indicates that activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in oxidative stress-induced cardiomyocyte apoptosis during ACS. In this study, we examined whether atorvastatin inhibits H2O2-induced LOX-1 expression and H9c2 cardiomyocyte apoptosis, and investigated the underlying signaling pathway. Treatment of H9c2 cardiomyocytes with H2O2 resulted in elevated expression of LOX-1 mRNA and protein, as well as increased caspase-3 and -9 protein expression and cell apoptosis. H2O2-induced LOX-1 expression, caspase protein expression, and cardiomyocyte apoptosis were attenuated by pretreatment with atorvastatin. Atorvastatin activated H2O2-inhibited phosphorylation of Akt in a concentration-dependent manner. The Akt inhibitor, LY294002, inhibited the effect of atorvastatin on inducing Akt phosphorylation and on suppressing H2O2-mediated caspase up-regulation and cell apoptosis. These findings indicate that atorvastatin protects cardiomyocyte from oxidative stress via inhibition of LOX-1 expression and apoptosis, and that activation of H2O2-inhibited phosphorylation of Akt may play an important role in the protective function of atorvastatin.

  5. Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

    SciTech Connect

    Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi; Zhang, Qunye; Li, Guorong

    2015-03-13

    As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.

  6. Inhibition of pyrite oxidation by surface coating: a long-term field study.

    PubMed

    Kang, Chan-Ung; Jeon, Byong-Hun; Park, Seong-Sook; Kang, Jin-Soo; Kim, Kang-Ho; Kim, Dong-Kwan; Choi, Ui-Kyu; Kim, Sun-Joon

    2016-10-01

    Pyrite and other iron sulfides are readily oxidized by dissolved oxygen in aqueous phase, producing acidity and Fe(2+), which causes significant environmental problems. Applications of surface coating agents (Na2SiO3 and KH2PO4) were conducted at Boeun (Chungbuk, South Korea) outcrop site, and their efficiencies to inhibit the oxidation of sulfide minerals were monitored for a long-term period (449 days). The rock sample showed positive Net Acid Production Potential (NAPP = 20.23) and low Net Acid Generation pH (NAGpH = 2.42) values, suggesting that the rock sample was categorized in the potential acid-forming group. For the monitored time period (449 days), field study results showed that the application of Na2SiO3 effectively inhibited the pyrite oxidation as compared to KH2PO4. Na2SiO3 as a surface coating agent maintained pH 5-6 and reduced oxidation of pyrite surface up to 99.95 and 97.70 % indicated by Fe(2+) and SO4 (2-) release, respectively. The scanning electron microscope and energy-dispersive X-ray spectrometer analysis indicated that the morphology of rock surface was completely changed attributable to formation of iron silicate coating. The experimental results suggested that the treatment with Na2SiO3 was highly effective and it might be applicable on field for inhibition of iron sulfide oxidation.

  7. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Barbosa, Décio S; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-24

    Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress-dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-β and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease.

  8. Sulfhydryl oxidation overrides Mg(2+) inhibition of calcium-induced calcium release in skeletal muscle triads.

    PubMed Central

    Donoso, P; Aracena, P; Hidalgo, C

    2000-01-01

    We studied the effect of oxidation of sulfhydryl (SH) residues on the inhibition by Mg(2+) of calcium-induced calcium release (CICR) in triad-enriched sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle. Vesicles were either passively or actively loaded with calcium before eliciting CICR by dilution at pCa 4.6-4.4 in the presence of 1.2 mM free [ATP] and variable free [Mg(2+)]. Native triads exhibited a significant inhibition of CICR by Mg(2+), with a K(0.5) approximately 50 microM. Partial oxidation of vesicles with thimerosal produced a significant increase of release rate constants and initial release rates at all [Mg(2+)] tested (up to 1 mM), and shifted the K(0.5) value for Mg(2+) inhibition to 101 or 137 microM in triads actively or passively loaded with calcium, respectively. Further oxidation of vesicles with thimerosal completely suppressed the inhibitory effect of [Mg(2+)] on CICR, yielding initial rates of CICR of 2 micromol/(mg x s) in the presence of 1 mM free [Mg(2+)]. These effects of oxidation on CICR were fully reversed by SH reducing agents. We propose that oxidation of calcium release channels, by decreasing markedly the affinity of the channel inhibitory site for Mg(2+), makes CICR possible in skeletal muscle. PMID:10866954

  9. Ultrahigh Temperature Capacitive Pressure Sensor

    NASA Technical Reports Server (NTRS)

    Harsh, Kevin

    2014-01-01

    Robust, miniaturized sensing systems are needed to improve performance, increase efficiency, and track system health status and failure modes of advanced propulsion systems. Because microsensors must operate in extremely harsh environments, there are many technical challenges involved in developing reliable systems. In addition to high temperatures and pressures, sensing systems are exposed to oxidation, corrosion, thermal shock, fatigue, fouling, and abrasive wear. In these harsh conditions, sensors must be able to withstand high flow rates, vibration, jet fuel, and exhaust. In order for existing and future aeropropulsion turbine engines to improve safety and reduce cost and emissions while controlling engine instabilities, more accurate and complete sensor information is necessary. High-temperature (300 to 1,350 C) capacitive pressure sensors are of particular interest due to their high measurement bandwidth and inherent suitability for wireless readout schemes. The objective of this project is to develop a capacitive pressure sensor based on silicon carbon nitride (SiCN), a new class of high-temperature ceramic materials, which possesses excellent mechanical and electric properties at temperatures up to 1,600 C.

  10. Online capacitive densitometer

    DOEpatents

    Porges, K.G.

    1988-01-21

    This invention is an apparatus for measuring fluid density of mixed phase fluid flow. The apparatus employs capacitive sensing of the mixed phased flow combined with means for uniformizing the electric field between the capacitor plates to account for flow line geometry. From measurement of fluid density, the solids feedrate can be ascertained. 7 figs.

  11. Steerable Capacitive Proximity Sensor

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

    Steerable capacitive proximity sensor of "capaciflector" type based partly on sensing units described in GSC-13377 and GSC-13475. Position of maximum sensitivity adjusted without moving sensor. Voltage of each driven shield adjusted separately to concentrate sensing electric field more toward one side or other.

  12. Digital capacitance measuring system

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The hardware phase of a digital capacitance measuring system is presented with the major emphasis placed on the electrical design and operation. Test results are included of the three units fabricated. The system's interface is applicable to existing requirements for the space shuttle vehicle.

  13. Online capacitive densitometer

    DOEpatents

    Porges, Karl G.

    1990-01-01

    This invention is an apparatus for measuring fluid density of mixed phase fluid flow. The apparatus employs capacitive sensing of the mixed phased flow combined with means for uniformizing the electric field between the capacitor plates to account for flow line geometry. From measurement of fluid density, the solids feedrate can be ascertained.

  14. Nitric oxide inhibits irreversibly P815 cell proliferation: involvement of potassium channels.

    PubMed

    Costa, R S A; Assreuy, J

    2002-12-01

    Nitric oxide (NO) has been shown to inhibit both normal and cancer cell proliferation. Potassium channels are involved in cell proliferation and, as NO activates these channels, we investigated the effect of NO on the proliferation of murine mastocytoma cell lines and the putative involvement of potassium channels. NO (in the form of NO donors) caused dose-dependent inhibition of cell proliferation in the P815 cell line inducing growth arrest in the mitosis phase. Incubation with NO donor for 4 or 24 h had a similar inhibitory effect on cell proliferation, indicating that this effect is irreversible. The inhibitory effect of NO was completely prevented by the blockade of voltage- and calcium-dependent potassium channels, but not by blockade of ATP-dependent channels. NO inhibition of cell proliferation was unaffected by guanylate cyclase and by cytoskeleton disruptors. Therefore, NO inhibits cell proliferation irreversibly via a potassium channel-dependent but guanylate cyclase-independent pathway in murine mastocytoma cells.

  15. Melatonin inhibits snake venom and antivenom induced oxidative stress and augments treatment efficacy.

    PubMed

    Sharma, Rachana D; Katkar, Gajanan D; Sundaram, Mahalingam S; Swethakumar, Basavarajaiah; Girish, Kesturu S; Kemparaju, Kempaiah

    2017-05-01

    Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potential for enhancing the existing snakebite therapy. The combined treatment of antivenom+melatonin would prevent the upsurge of oxidative stress as well as minimize the antivenom load. Thus the investigation offers immense scope for physicians and toxinologists to reinvestigate, design new strategies and think beyond the conventional mode of antivenom therapy.

  16. Ultrafine nickel oxide quantum dots enbedded with few-layer exfoliative graphene for an asymmetric supercapacitor: Enhanced capacitances by alternating voltage

    NASA Astrophysics Data System (ADS)

    Jing, Mingjun; Wang, Chiwei; Hou, Hongshuai; Wu, Zhibin; Zhu, Yirong; Yang, Yingchang; Jia, Xinnan; Zhang, Yan; Ji, Xiaobo

    2015-12-01

    A green and one-step method of electrochemical alternating voltage has been utilized to form NiO quantum dots/graphene flakes (NiO-dots/Gh) for supercapacitor applications. NiO quantum dots (∼3 nm) are uniformly deposited on few-layer graphene surfaces by oxygen functional groups on graphene surface that is naturally utilized to bridge NiO and graphene through Ni-O-C bands, which exhibits outstanding specific capacitance 1181.1 F g-1 at a current density of 2.1 A g-1 and rate behavior 66.2% at 42 A g-1 as NiO dots can be fleetly wired up to current collector through the underlying graphene two-dimensional layers. The NiO-dots/Gh composite is further undertaken in asymmetric supercapacitors with high energy density (27.3 Wh kg-1 at 1562.6 W kg-1).

  17. Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

    PubMed Central

    La Fountaine, Michael F; Radulovic, Miroslav; Cardozo, Christopher P; Spungen, Ann M; DeMeersman, Ronald E; Bauman, William A

    2009-01-01

    Background/Objective: To improve our understanding of the lower-leg vascular responses of nitric oxide synthase inhibition in persons with tetraplegia. Participants: Six people with chronic tetraplegia and 6 age-matched controls. Methods: Lower-leg relative vascular resistance and venous volume variation were obtained by venous occlusion plethysmography and blood pressure by auscultation at baseline. Postintravenous infusion of the nitric oxide synthase inhibitor NG-nitro-l-arginine-methyl-ester (1 mg·kg−1) or placebo on separate days. Results: At baseline in the group with tetraplegia compared with controls, mean arterial pressure and relative vascular resistance of the leg were significantly lower. After nitric oxide synthase inhibition, mean arterial pressure and lower leg vascular resistance were significantly elevated in both groups. There were no group or intervention differences in venous volume variation. Conclusion: These preliminary results suggest that nitric oxide synthase inhibition with 1 mg·kg−1 NG-nitro-l-arginine-methyl-ester normalizes seated blood pressure and lower leg vascular resistance to control group baseline levels. PMID:20025149

  18. Effects of inhibition of. beta. -oxidation on tissue kinetics of C-11 palmitate in normal myocardium

    SciTech Connect

    Wijns, W.; Schwaiger, M.; Huang, S.C.; Selin, C.; Grover-McKay, M.; Hansen, H.; Phelps, M.; Schelbert, H.R.

    1985-05-01

    C-11 palmitate (CPA) clears from myocardium biexponentially. The late slow tissue clearance curve component is thought to represent tracer deposited in the endogenous lipid pool. The early rapid component is thought to be related to oxidation of CPA. The nature of the curve components can be clarified by specific inhibition of individual metabolic steps, e.g., ..beta..-oxidation. Therefore, 11 dogs were studied at control and again after inhibition of carnitine acyltransferase I with iv. tetradecylglycidic acid (TDGA; 10 mg/kg). CPA was injected into the coronary circulation. Myocardial time activity curves (TAC) were analyzed by least square fitting. After TDGA, the late slow phase was unchanged (RS=32 +- 9%; T=336 +- 146 min) but the early rapid phase was reduced (RS=18 +- 8%; T=2.9 +- 1.4 min) while 50 +- 9% of extracted CPA diffused back (T=10.8 +- 3.6 sec). Thus, inhibition of ..beta..-oxidation shifted substrate usage from FFA to carbohydrates, had no effect on esterification of CPA but enhanced its back diffusion from myocardium. As discussed in this paper the decline of the early rapid phase indicates its relationship to CPA oxidation.

  19. Inhibition of apple polyphenol oxidase activity by procyanidins and polyphenol oxidation products.

    PubMed

    Le Bourvellec, Carine; Le Quéré, Jean-Michel; Sanoner, Philippe; Drilleau, Jean-François; Guyot, Sylvain

    2004-01-14

    The rate of consumption of dissolved oxygen by apple polyphenol oxidase in cider apple juices did not correlate with polyphenol oxidase activity in the fruits and decreased faster than could be explained by the decrease of its polyphenolic substrates. The kinetics parameters of a crude polyphenol oxidase extract, prepared from apple (Braeburn cultivar), were determined using caffeoylquinic acid as a substrate. Three apple procyanidin fractions of n 80, 10.5, and 4 were purified from the parenchyma of cider apples of various cultivars. Procyanidins, caffeoylquinic acid, (-)-epicatechin, and a mixture of caffeoylquinic acid and (-)-epicatechin were oxidized by reaction with caffeoylquinic acid o-quinone in order to form oxidation products. All the fractions were evaluated for their inhibitory effect on PPO activity. Native procyanidins inhibited polyphenol oxidase activity, the inhibition intensity increasing with n. The polyphenol oxidase activity decreased by 50% for 0.026 g/L of the fraction of n 80, 0.17 g/L of the fraction of n 10.5, and 1 g/L of the fraction of n 4. The inhibitory effect of oxidized procyanidins was twice that of native procyanidins. Oxidation products of caffeoylquinic acid and (-)-epicatechin also inhibited polyphenol oxidase.

  20. Zinc inhibits oxidative stress-induced iron signaling and apoptosis in Caco-2 cells.

    PubMed

    Kilari, Sreenivasulu; Pullakhandam, Raghu; Nair, K Madhavan

    2010-04-01

    Studies in humans and animals have suggested negative interactions of iron and zinc during their intestinal absorption. Further, zinc seems to prevent iron-induced oxidative damage in rats, which was hypothesized to be through the modulation of the intracellular iron signaling pathway. The aim of this study was, therefore, to understand the effects of zinc on oxidant-induced iron signaling and cell death in human enterocyte-like Caco-2 cells. We demonstrate that zinc decreases glucose/glucose oxidase (H(2)O(2)-generating system)-induced iron uptake and inhibits iron-regulatory protein 1 activation and divalent metal ion transporter 1 expression. There was also a concomitant decrease in oxidant-induced intracellular labile iron and restoration of ferritin and metallothionein expression. Further, zinc enhanced the Bcl-2/Bax ratio and reduced caspase-3 activity, leading to inhibition of apoptosis. Interestingly, bathophenanthroline disulfonic acid, an extracellular iron chelator, emulated the effects of zinc except for the reduced ferritin levels. These results suggest that zinc inhibits apoptosis by reducing oxidant-induced iron signaling in Caco-2 cells.

  1. Cyclin D1 represses peroxisome proliferator-activated receptor alpha and inhibits fatty acid oxidation

    PubMed Central

    Hanse, Eric A.; Mashek, Douglas G.; Mashek, Mara T.; Hendrickson, Anna M.; Mullany, Lisa K.; Albrecht, Jeffrey H.

    2016-01-01

    Cyclin D1 is a cell cycle protein that promotes proliferation by mediating progression through key checkpoints in G1 phase. It is also a proto-oncogene that is commonly overexpressed in human cancers. In addition to its canonical role in controlling cell cycle progression, cyclin D1 affects other aspects of cell physiology, in part through transcriptional regulation. In this study, we find that cyclin D1 inhibits the activity of a key metabolic transcription factor, peroxisome proliferator-activated receptor α (PPARα), a member of nuclear receptor family that induces fatty acid oxidation and may play an anti-neoplastic role. In primary hepatocytes, cyclin D1 inhibits PPARα transcriptional activity and target gene expression in a cdk4-independent manner. In liver and breast cancer cells, knockdown of cyclin D1 leads to increased PPARα transcriptional activity, expression of PPARα target genes, and fatty acid oxidation. Similarly, cyclin D1 depletion enhances binding of PPARα to target sequences by chromatin immunoprecipitation. In proliferating hepatocytes and regenerating liver in vivo, induction of endogenous cyclin D1 is associated with diminished PPARα activity. Cyclin D1 expression is both necessary and sufficient for growth factor-mediated repression of fatty acid oxidation in proliferating hepatocytes. These studies indicate that in addition to playing a pivotal role in cell cycle progression, cyclin D1 represses PPARα activity and inhibits fatty acid oxidation. Our findings establish a new link between cyclin D1 and metabolism in both tumor cells and physiologic hepatocyte proliferation. PMID:27351284

  2. Cyclin D1 represses peroxisome proliferator-activated receptor alpha and inhibits fatty acid oxidation.

    PubMed

    Kamarajugadda, Sushama; Becker, Jennifer R; Hanse, Eric A; Mashek, Douglas G; Mashek, Mara T; Hendrickson, Anna M; Mullany, Lisa K; Albrecht, Jeffrey H

    2016-07-26

    Cyclin D1 is a cell cycle protein that promotes proliferation by mediating progression through key checkpoints in G1 phase. It is also a proto-oncogene that is commonly overexpressed in human cancers. In addition to its canonical role in controlling cell cycle progression, cyclin D1 affects other aspects of cell physiology, in part through transcriptional regulation. In this study, we find that cyclin D1 inhibits the activity of a key metabolic transcription factor, peroxisome proliferator-activated receptor α (PPARα), a member of nuclear receptor family that induces fatty acid oxidation and may play an anti-neoplastic role. In primary hepatocytes, cyclin D1 inhibits PPARα transcriptional activity and target gene expression in a cdk4-independent manner. In liver and breast cancer cells, knockdown of cyclin D1 leads to increased PPARα transcriptional activity, expression of PPARα target genes, and fatty acid oxidation. Similarly, cyclin D1 depletion enhances binding of PPARα to target sequences by chromatin immunoprecipitation. In proliferating hepatocytes and regenerating liver in vivo, induction of endogenous cyclin D1 is associated with diminished PPARα activity. Cyclin D1 expression is both necessary and sufficient for growth factor-mediated repression of fatty acid oxidation in proliferating hepatocytes. These studies indicate that in addition to playing a pivotal role in cell cycle progression, cyclin D1 represses PPARα activity and inhibits fatty acid oxidation. Our findings establish a new link between cyclin D1 and metabolism in both tumor cells and physiologic hepatocyte proliferation.

  3. Nitric oxide inhibits c-Jun DNA binding by specifically targeted S-glutathionylation.

    PubMed

    Klatt, P; Molina, E P; Lamas, S

    1999-05-28

    This study addresses potential molecular mechanisms underlying the inhibition of the transcription factor c-Jun by nitric oxide. We show that in the presence of the physiological sulfhydryl glutathione nitric oxide modifies the two cysteine residues contained in the DNA binding module of c-Jun in a selective and distinct way. Although nitric oxide induced the formation of an intermolecular disulfide bridge between cysteine residues in the leucine zipper site of c-Jun monomers, this same radical directed the covalent incorporation of stoichiometric amounts of glutathione to a single conserved cysteine residue in the DNA-binding site of the protein. We found that covalent dimerization of c-Jun apparently did not affect its DNA binding activity, whereas the formation of a mixed disulfide with glutathione correlated well with the inhibition of transcription factor binding to DNA. Furthermore, we provide experimental evidence that nitric oxide-induced S-glutathionylation and inhibition of c-Jun involves the formation of S-nitrosoglutathione. In conclusion, our results support the reversible formation of a mixed disulfide between glutathione and c-Jun as a potential mechanism by which nitrosative stress may be transduced into a functional response at the level of transcription.

  4. Enzymatic oxidation of phthalazine with guinea pig liver aldehyde oxidase and liver slices: inhibition by isovanillin.

    PubMed

    Panoutsopoulos, Georgios I; Beedham, Christine

    2004-01-01

    The enzymes aldehyde oxidase and xanthine oxidase catalyze the oxidation of a wide range of N-heterocycles and aldehydes. These enzymes are widely known for their role in the metabolism of N-heterocyclic xenobiotics where they provide a protective barrier by aiding in the detoxification of ingested nitrogen-containing heterocycles. Isovanillin has been shown to inhibit the metabolism of aromatic aldehydes by aldehyde oxidase, but its inhibition towards the heterocyclic compounds has not been studied. The present investigation examines the oxidation of phthalazine in the absence and in the presence of the inhibitor isovanillin by partially purified aldehyde oxidase from guinea pig liver. In addition, the interaction of phthalazine with freshly prepared guinea pig liver slices, both in the absence and presence of specific inhibitors of several liver oxidizing enzymes, was investigated. ldehyde oxidase rapidly converted phthalazine into 1-phthalazinone, which was completely inhibited in the presence of isovanillin (a specific inhibitor of aldehyde oxidase). In freshly prepared liver slices, phthalazine was also rapidly converted to 1-phthalazinone. The formation of 1-phthalazinone was completely inhibited by isovanillin, whereas disulfiram (a specific inhibitor of aldehyde dehydrogenase) only inhibited 1-phthalazinone formation by 24% and allopurinol (a specific inhibitor of xanthine oxidase) had little effect. Therefore, isovanillin has been proved as an inhibitor of the metabolism of heterocyclic substrates, such as phthalazine, by guinea pig liver aldehyde oxidase, since it had not been tested before. Thus it would appear from the inhibitor results that aldehyde oxidase is the predominant enzyme in the oxidation of phthalazine to 1-phthalazinone in freshly prepared guinea pig liver slices, whereas xanthine oxidase only contributes to a small extent and aldehyde dehydrogenase does not take any part.

  5. Cranberries inhibit LDL oxidation and induce LDL receptor expression in hepatocytes.

    PubMed

    Chu, Yi-Fang; Liu, Rui Hai

    2005-08-26

    Cardiovascular disease (CVD) is the leading cause of death in most industrialized countries. Cranberries were evaluated for their potential roles in dietary prevention of CVD. Cranberry extracts were found to have potent antioxidant capacity preventing in vitro LDL oxidation with increasing delay and suppression of LDL oxidation in a dose-dependent manner. The antioxidant activity of 100 g cranberries against LDL oxidation was equivalent to 1000 mg vitamin C or 3700 mg vitamin E. Cranberry extracts also significantly induced expression of hepatic LDL receptors and increased intracellular uptake of cholesterol in HepG2 cells in vitro in a dose-dependent manner. This suggests that cranberries could enhance clearance of excessive plasma cholesterol in circulation. We propose that additive or synergistic effects of phytochemicals in cranberries are responsible for the inhibition of LDL oxidation, the induced expression of LDL receptors, and the increased uptake of cholesterol in hepatocytes.

  6. LPS-Induced Macrophage Activation and Plasma Membrane Fluidity Changes are Inhibited Under Oxidative Stress.

    PubMed

    de la Haba, Carlos; Morros, Antoni; Martínez, Paz; Palacio, José R

    2016-12-01

    Macrophage activation is essential for a correct and efficient response of innate immunity. During oxidative stress membrane receptors and/or membrane lipid dynamics can be altered, leading to dysfunctional cell responses. Our aim is to analyze membrane fluidity modifications and cell function under oxidative stress in LPS-activated macrophages. Membrane fluidity of individual living THP-1 macrophages was evaluated by the technique two-photon microscopy. LPS-activated macrophage function was determined by TNFα secretion. It was shown that LPS activation causes fluidification of macrophage plasma membrane and production of TNFα. However, oxidative stress induces rigidification of macrophage plasma membrane and inhibition of cell activation, which is evidenced by a decrease of TNFα secretion. Thus, under oxidative conditions macrophage proinflammatory response might develop in an inefficient manner.

  7. New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

    PubMed Central

    Mitra, Joy; Guerrero, Erika N.; Hegde, Pavana M.; Wang, Haibo; Boldogh, Istvan; Rao, Kosagi Sharaf; Mitra, Sankar; Hegde, Muralidhar L.

    2014-01-01

    The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases. PMID:25036887

  8. Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression

    PubMed Central

    Eberlein, Michael; Scheibner, Kara A; Black, Katharine E; Collins, Samuel L; Chan-Li, Yee; Powell, Jonathan D; Horton, Maureen R

    2008-01-01

    Background The balance between reactive oxygen species (ROS) and endogenous anti-oxidants is important in maintaining healthy tissues. Excessive ROS states occur in diseases such as ARDS and Idiopathic Pulmonary Fibrosis. Redox imbalance breaks down the extracellular matrix component hyaluronan (HA) into fragments that activate innate immune responses and perpetuate tissue injury. HA fragments, via a TLR and NF-κB pathway, induce inflammatory gene expression in macrophages and epithelial cells. NAC and DMSO are potent anti-oxidants which may help balance excess ROS states. Methods We evaluated the effect of H2O2, NAC and DMSO on HA fragment induced inflammatory gene expression in alveolar macrophages and epithelial cells. Results NAC and DMSO inhibit HA fragment-induced expression of TNF-α and KC protein in alveolar and peritoneal macrophages. NAC and DMSO also show a dose dependent inhibition of IP-10 protein expression, but not IL-8 protein, in alveolar epithelial cells. In addition, H2O2 synergizes with HA fragments to induce inflammatory genes, which are inhibited by NAC. Mechanistically, NAC and DMSO inhibit HA induced gene expression by inhibiting NF-κB activation, but NAC had no influence on HA-fragment-AP-1 mediated gene expression. Conclusion ROS play a central role in a pathophysiologic "vicious cycle" of inflammation: tissue injury generates ROS, which fragment the extracellular matrix HA, which in turn synergize with ROS to activate the innate immune system and further promote ROS, HA fragment generation, inflammation, tissue injury and ultimately fibrosis. The anti-oxidants NAC and DMSO, by inhibiting the HA induced inflammatory gene expression, may help re-balance excessive ROS induced inflammation. PMID:18986521

  9. Inhibition of oxidative phosphorylation in ascites tumor mitochondria and cells by intramitochondrial Ca2+.

    PubMed

    Villalobo, A; Lehninger, A L

    1980-03-25

    Accumulation of Ca2+ (+ phosphate) by respiring mitochondria from Ehrlich ascites or AS30-D hepatoma tumor cells inhibits subsequent phosphorylating respiration in response to ADP. The respiratory chain is still functional since a proton-conducting uncoupler produces a normal stimulation of electron transport. The inhibition of phosphorylating respiration is caused by intramitochondrial Ca2+ (+ phosphate). ATP + Mg2+ together, but not singly, prevents the inhibitory action of Ca2+. Neither AMP, GTP, GDP, nor any other nucleoside 5'-triphosphate or 5'-diphosphate could replace ATP in this effect. Phosphorylating respiration on NAD(NADP)-linked substrates was much more susceptible to the inhibitory effect of intramitochondrial Ca2+ than succinate-linked respiration. Significant inhibition of oxidative phosphorylation is given by the endogenous Ca2+ present in freshly isolated tumor mitochondria. The phosphorylating respiration of permeabilized Ehrlich ascites tumor cells is also inhibited by Ca2+ accumulated by the mitochondria in situ. Possible causes of the Ca2+-induced inhibition of oxidative phosphorylation are considered.

  10. Inhibition of inducible nitric oxide synthase and osteoclastic differentiation by Atractylodis Rhizoma Alba extract

    PubMed Central

    Choi, Sung-Ho; Kim, Sung-Jin

    2014-01-01

    Background: Atractylodis Rhizoma Alba (ARA) has been used in Korean folk medicine for constipation, dizziness, and anticancer agent. In the present study, we performed to test whether the methanolic extract of ARA has antioxidant and antiosteoclastogenesis activity in RAW 264.7 macrophage cells. Materials and Methods: Antioxidant capacities were tested by measuring free radical scavenging activity, nitric oxide (NO) levels, reducing power, and inducible nitric oxide synthase (iNOS) expression in response to lipopolysaccharides (LPS). Antiosteoclastogenesis activity was evaluated by performing tartrate-resistant acid phosphatase assay in RAW 264.7 macrophage cells. Results: The extract exerted significant 1,1-diphenyl-2-picrylhydrazyl and NO radical scavenging activity, and it exerted dramatic reducing power. Induction of iNOS and NO by LPS in RAW 264.7 cells was significantly inhibited by the extract, suggesting that the ARA extract inhibits NO production by suppressing iNOS expression. Strikingly, the ARA extracts substantially inhibited the receptor activator of NF-κB ligand-induced osteclastic differentiation of LPS-activated RAW 264.7 cells. The ARA extract contains a significant amount of antioxidant components, including phenolics, flavonoids and anthocyanins. Conclusion: These results suggest that the methanolic extract of ARA exerts significant antioxidant activities potentially via inhibiting free radicals and iNOS induction, thereby leading to the inhibition of osteoclastogenesis. PMID:25298665

  11. Field-Scale Inhibition and Recovery of Atmospheric-Methane Oxidation in Soil

    NASA Astrophysics Data System (ADS)

    Schroth, M. H.; Dax, A.; Genter, F.; Henneberger, R.

    2015-12-01

    Aerobic methane (CH4) oxidation in upland soils is the only known terrestrial sink for atmospheric CH4. It is mediated by methane-oxidizing bacteria (MOB) that possess a high-affinity form of the enzyme methane monooxygenase (MMO), allowing utilization of CH4 at near-atmospheric, low concentrations (≤ 1.9 µL/L). As cultivation attempts for high-affinity MOB have shown little success to date, there remains much speculation regarding their functioning in different environmental systems. For quantification of microbial functions at the field scale, inhibition experiments are often used as a control and to verify that observed substrate turnover is microbially mediated. Targeting MMO, several compounds have been proposed as inhibitors of CH4 oxidation. However, previous inhibition experiments were mostly conducted in systems dominated by low-affinity MOB, which mediate CH4 oxidation at elevated CH4 concentrations. On the contrary, inhibition experiments targeting high-affinity MOB are scare, particularly at the field scale. We present results of field-scale experiments to investigate effectiveness of and recovery from inhibition of atmospheric CH4 oxidation using the competitive inhibitors CH3F and CH2F2, as well as the non-competitive inhibitor C2H2. The latter is of particular interest, because C2H2 irreversibly binds to MMO, requiring de-novo synthesis of MMO for recovery of CH4 oxidation activity. Experiments were conducted during both winter and summer seasons in a sandy soil. Atmospheric CH4 oxidation was quantified in regular intervals at reference and treatment locations using the soil-profile method with concurrent measurements of soil-water contents and -temperature. Whereas C2H2 inhibition was highly effective in both seasons, the time required for recovery to the level of the reference location was much shorter during the summer experiment (~1 mo compared with 4 mo during winter). Our data provide new insights into the physiology of high-affinity MOB.

  12. Inhibition of human LDL oxidation by the neuroprotective drug l-deprenyl.

    PubMed

    Thomas, Tom; Bhavnani, Bhagu R; Thomas, Prem

    2002-03-01

    L-deprenyl (Selegiline) used in the treatment of Parkinson's and Alzheimer's disease also enhances longevity. Oxidized low density lipoprotein promotes atherosclerosis and is toxic to both vascular and neural tissue. The reported association between vascular dysfunction and neurodegenerative diseases prompted us to investigate the effect of l-deprenyl, a MAO-B inhibitor, on low density lipoprotein (LDL) oxidation. LDL was isolated from freshly collected blood and the kinetics of copper induced oxidation of LDL was monitored continuously by spectrophotometry. Oral administration (10 mg) or in vitro (2.8 to 84 microM) addition of l-deprenyl inhibited oxidation of LDL isolated from healthy men and post-menopausal women. This is the first report demonstrating that the antioxidant action of l-deprenyl may be antiatherogenic and cardioprotective. Such an action could contribute to reported extension of life span associated with long-term administration of the drug. In conjunction with inhibition of LDL oxidation, l-deprenyl is unique in that it demonstrates protective effects on both vascular and neuronal tissue. Prophylactic use of low doses of l-deprenyl may accord protection against vascular and neurodegenerative diseases associated with aging.

  13. Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

    PubMed Central

    Murugesan, G; Fox, P L

    1996-01-01

    Endothelial cell (EC) movement is required for the development and repair of blood vessels. We have previously shown that LDL oxidized by transition metals almost completely suppressed the wound-healing migratory response of vascular EC in vitro. We now report that lysophosphatidylcholine (lysoPC), a lipid component of oxidized LDL, has an important role in the antimigratory activity of the lipoprotein. Purified 1-palmitoyl lysoPC inhibited movement with a half-maximal activity at 12-15 micrometers, and near complete inhibition at 20 micrometers; the inhibitory concentration of lysoPC was consistent with its abundance in oxidized LDL. The inhibition was not due to cytotoxicity since protein synthesis was unaffected and since EC movement was restored after removal of lysoPC. Lysophospholipid activity was dependent on lipid structure. LysoPC's containing 1-position C16 or C18 saturated fatty acids were antimigratory, but those containing C < or = 14 saturated fatty acids or polyunsaturated fatty acids were not. The activity of 1-palmitoyl lysolipids with various head groups was examined. Lysophosphatidylinositol was more antimigratory than lysophosphatidylglycerol and lysophosphatidylcholine, which were more potent than lysophosphatidylserine and lysophosphatidylethanolamine. Monoglyceride was inactive while lysophosphatidate had promigratory activity. These results are consistent with head group size rather than charge as a critical determinant of activity. To show that lysophospholipids within an intact lipoprotein were active, LDL was treated with bee venom phospholipase A2 (PLA2). The modified lipoprotein inhibited EC movement to the same extent as iron-oxidized LDL and antimigratory activity correlated with the amount of lysoPC formed. To determine antimigratory activity of lysoPC present in oxidized LDL, lipid extracts from oxidized LDL were fractionated by normal phase HPLC. The fraction comigrating with lysoPC had nearly the same activity as the total extract

  14. Capacitive deionization of seawater

    SciTech Connect

    Farmer, J.C.; Fix, D.V.; Mack, G.V.

    1995-10-01

    Capacitive deionization with carbon aerogel electrodes is an efficient and economical new process for removing salt and impurities from water. Carbon aerogel is a material that enables the successful purification of water because of its high surface area, optimum pore size, and low electrical resistivity. The electrodes are maintained at a potential difference of about one volt; ions are removed from the water by the imposed electrostatic field and retained on the electrode surface until the polarity is reversed. The capacitive deionization of water with a stack of carbon aerogel electrodes has been successfully demonstrated. The overall process offers advantages when compared to conventional water-purification methods, requiring neither pumps, membranes, distillation columns, nor thermal heaters. Consequently, the overall process is both robust and energy efficient. The current state of technology development, commercialization, and potential applications of this process are reviewed.

  15. Capacitive skin characterization

    NASA Technical Reports Server (NTRS)

    Mcconnell, Robert; Manzo, Michael

    1992-01-01

    NASA is currently involved in research that utilizes a capacitive sensor that is used for proximity detection of objects. This sensor is sensitive to conductive and dielectric materials including metal objects and humans. The range of the sensor has been found to be about twelve inches. It is the goal of this research project to further characterize the sensor so that it can be tailored to specific requirements. The characterization of the sensor should be with respect to shield size, sensor size, object size, and object distance. The method of finite elements to calculate the capacitance of the sensor while varying different parameters was used. Each of the parameters was varied in turn, often by selecting data points from different runs. The plotted results are shown and an apparent functionality developed for each.

  16. Inhibition of a biological sulfide oxidation under haloalkaline conditions by thiols and diorgano polysulfanes.

    PubMed

    Roman, Pawel; Lipińska, Joanna; Bijmans, Martijn F M; Sorokin, Dimitry Y; Keesman, Karel J; Janssen, Albert J H

    2016-09-15

    A novel approach has been developed for the simultaneous description of reaction kinetics to describe the formation of polysulfide and sulfate anions from the biological oxidation of hydrogen sulfide (H2S) using a quick, sulfide-dependent respiration test. Next to H2S, thiols are commonly present in sour gas streams. We investigated the inhibition mode and the corresponding inhibition constants of six thiols and the corresponding diorgano polysulfanes on the biological oxidation of H2S. A linear relationship was found between the calculated IC50 values and the lipophilicity of the inhibitors. Moreover, a mathematical model was proposed to estimate the biomass activity in the absence and presence of sulfurous inhibitors. The biomass used in the respiration tests originated from a full-scale biodesulfurization reactor. A microbial community analysis of this biomass revealed that two groups of microorganism are abundant, viz. Ectothiorhodospiraceae and Piscirickettsiaceae.

  17. Polarized cell motility induces hydrogen peroxide to inhibit cofilin via cysteine oxidation.

    PubMed

    Cameron, Jenifer M; Gabrielsen, Mads; Chim, Ya Hua; Munro, June; McGhee, Ewan J; Sumpton, David; Eaton, Philip; Anderson, Kurt I; Yin, Huabing; Olson, Michael F

    2015-06-01

    Mesenchymal cell motility is driven by polarized actin polymerization [1]. Signals at the leading edge recruit actin polymerization machinery to promote membrane protrusion, while matrix adhesion generates tractive force to propel forward movement. To work effectively, cell motility is regulated by a complex network of signaling events that affect protein activity and localization. H2O2 has an important role as a diffusible second messenger [2], and mediates its effects through oxidation of cysteine thiols. One cell activity influenced by H2O2 is motility [3]. However, a lack of sensitive and H2O2-specific probes for measurements in live cells has not allowed for direct observation of H2O2 accumulation in migrating cells or protrusions. In addition, the identities of proteins oxidized by H2O2 that contribute to actin dynamics and cell motility have not been characterized. We now show, as determined by fluorescence lifetime imaging microscopy, that motile cells generate H2O2 at membranes and cell protrusions and that H2O2 inhibits cofilin activity through oxidation of cysteines 139 (C139) and 147 (C147). Molecular modeling suggests that C139 oxidation would sterically hinder actin association, while the increased negative charge of oxidized C147 would lead to electrostatic repulsion of the opposite negatively charged surface. Expression of oxidation-resistant cofilin impairs cell spreading, adhesion, and directional migration. These findings indicate that H2O2 production contributes to polarized cell motility through localized cofilin inhibition and that there are additional proteins oxidized during cell migration that might have similar roles.

  18. Autocrine inhibition of Na+/K(+)-ATPase by nitric oxide in mouse proximal tubule epithelial cells.

    PubMed Central

    Guzman, N J; Fang, M Z; Tang, S S; Ingelfinger, J R; Garg, L C

    1995-01-01

    An inducible nitric oxide synthase has recently been described in proximal tubule epithelium. To investigate the effects of proximal tubule NO on Na+/K(+)-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) followed by determinations of ouabain-sensitive ATPase activity. Na+/K(+)-ATPase activity decreased after 4 h of LPS/IFN gamma treatment, reaching maximal inhibition after 24 h (34% reduction in activity). The inhibition of Na+/K(+)-ATPase activity by LPS/IFN gamma was prevented by simultaneous incubation with N omega-nitro L-arginine and markedly blunted by removal of L-arginine from the medium. The NO donors sodium nitroprusside and SIN-1 also inhibited Na+/K(+)-ATPase activity to a similar extent than LPS/IFN gamma. However, treatment with 8-pCPT-cGMP only modestly reduced Na+/K(+)-ATPase activity. Interestingly, superoxide dismutase prevented the inhibitory effects of NO on Na+/K(+)-ATPase activity, suggesting a role for peroxynitrite in this inhibition. We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport. PMID:7537754

  19. Oxidative stress inhibits caveolin-1 palmitoylation and trafficking in endothelial cells

    NASA Technical Reports Server (NTRS)

    Parat, Marie-Odile; Stachowicz, Rafal Z.; Fox, Paul L.

    2002-01-01

    During normal and pathological conditions, endothelial cells (ECs) are subjected to locally generated reactive oxygen species, produced by themselves or by other vessel wall cells. In excess these molecules cause oxidative injury to the cell but at moderate levels they might modulate intracellular signalling pathways. We have investigated the effect of oxidative stress on the palmitoylation and trafficking of caveolin-1 in bovine aortic ECs. Exogenous H2O2 did not alter the intracellular localization of caveolin-1 in ECs. However, metabolic labelling experiments showed that H2O2 inhibited the trafficking of newly synthesized caveolin-1 to membrane raft domains. Several mechanisms potentially responsible for this inhibition were examined. Impairment of caveolin-1 synthesis by H2O2 was not responsible for diminished trafficking. Similarly, the inhibition was independent of H2O2-induced caveolin-1 phosphorylation as shown by the markedly different concentration dependences. We tested the effect of H2O2 on palmitoylation of caveolin-1 by the incorporation of [3H]palmitic acid. Exposure of ECs to H2O2 markedly inhibited the palmitoylation of caveolin-1. Comparable inhibition was observed after treatment of cells with H2O2 delivered either as a bolus or by continuous delivery with glucose and glucose oxidase. Kinetic studies showed that H2O2 did not alter the rate of caveolin-1 depalmitoylation but instead decreased the 'on-rate' of palmitoylation. Together these results show for the first time the modulation of protein palmitoylation by oxidative stress, and suggest a cellular mechanism by which stress might influence caveolin-1-dependent cell activities such as the concentration of signalling proteins and cholesterol trafficking.

  20. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction

    PubMed Central

    Samudio, Ismael; Harmancey, Romain; Fiegl, Michael; Kantarjian, Hagop; Konopleva, Marina; Korchin, Borys; Kaluarachchi, Kumar; Bornmann, William; Duvvuri, Seshagiri; Taegtmeyer, Heinrich; Andreeff, Michael

    2009-01-01

    The traditional view is that cancer cells predominately produce ATP by glycolysis, rather than by oxidation of energy-providing substrates. Mitochondrial uncoupling — the continuing reduction of oxygen without ATP synthesis — has recently been shown in leukemia cells to circumvent the ability of oxygen to inhibit glycolysis, and may promote the metabolic preference for glycolysis by shifting from pyruvate oxidation to fatty acid oxidation (FAO). Here we have demonstrated that pharmacologic inhibition of FAO with etomoxir or ranolazine inhibited proliferation and sensitized human leukemia cells — cultured alone or on bone marrow stromal cells — to apoptosis induction by ABT-737, a molecule that releases proapoptotic Bcl-2 proteins such as Bak from antiapoptotic family members. Likewise, treatment with the fatty acid synthase/lipolysis inhibitor orlistat also sensitized leukemia cells to ABT-737, which supports the notion that fatty acids promote cell survival. Mechanistically, we generated evidence suggesting that FAO regulates the activity of Bak-dependent mitochondrial permeability transition. Importantly, etomoxir decreased the number of quiescent leukemia progenitor cells in approximately 50% of primary human acute myeloid leukemia samples and, when combined with either ABT-737 or cytosine arabinoside, provided substantial therapeutic benefit in a murine model of leukemia. The results support the concept of FAO inhibitors as a therapeutic strategy in hematological malignancies. PMID:20038799

  1. Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening.

    PubMed

    Sun, Wen-xiao; Zheng, Hai-ya; Lan, Jun

    2015-11-01

    Existing evidences have emphasized an important role of oxidative stress in dexamethasone (Dex)-induced osteoblastic cell damages. Here, we investigated the possible anti-Dex activity of edaravone in osteoblastic cells, and studied the underlying mechanisms. We showed that edaravone dose-dependently attenuated Dex-induced death and apoptosis of established human or murine osteoblastic cells. Further, Dex-mediated damages to primary murine osteoblasts were also alleviated by edaravone. In osteoblastic cells/osteoblasts, Dex induced significant oxidative stresses, tested by increased levels of reactive oxygen species and lipid peroxidation, which were remarkably inhibited by edaravone. Meanwhile, edaravone repressed Dex-induced mitochondrial permeability transition pore (mPTP) opening, or mitochondrial membrane potential reduction, in osteoblastic cells/osteoblasts. Significantly, edaravone-induced osteoblast-protective activity against Dex was alleviated with mPTP inhibition through cyclosporin A or cyclophilin-D siRNA. Together, we demonstrate that edaravone protects osteoblasts from Dex-induced damages probably through inhibiting oxidative stresses and following mPTP opening.

  2. The origin of grain boundary capacitance in highly doped ceria.

    PubMed

    Souza, Eduardo Caetano C; Goodenough, John B

    2016-02-17

    The origin of a grain-boundary capacitance in mixed oxide-ion/electronic conductors has been investigated for the case of Ce0.8Sm0.2O1.9-δ using a.c. impedance spectroscopy under low pO2 from 250 to 400 °C. The observed capacitance is interpreted in terms of Ce(III):4f(1) electrons first introduced into the grains and not into the grain boundaries.

  3. Analyzing the revolution of anaerobic ammonium oxidation (anammox) performance and sludge characteristics under zinc inhibition.

    PubMed

    Zhang, Qian-Qian; Zhang, Zheng-Zhe; Guo, Qiong; Wang, Jiao-Jiao; Wang, Hui-Zhong; Jin, Ren-Cun

    2015-04-01

    In the present study, the short- and long-term effects of Zn(II) on the anaerobic ammonium oxidation (anammox) performance and sludge characteristics were evaluated. The anammox activity decreased with increasing Zn(II) concentration and pre-exposure time in short-term tests. The half maximal inhibitory concentration (IC50) of Zn(II) was found to be 25.0 mg L(-1). The 24 and 48-h pre-exposure time was a restricted factor impacting the anammox activity, and washing the inhibited sludge with buffer solution only worked under 0 and 24-h pre-exposure time. The anammox sludge could tolerate 5 mg L(-1) Zn(II) but was suppressed at 8 mg L(-1). The inhibited performance could be remitted, as the combination strategies were applied, and after the short term of recovery period, the inhibited sludge characteristics were remitted to the normal.

  4. Idesolide inhibits the adipogenic differentiation of mesenchymal cells through the suppression of nitric oxide production.

    PubMed

    Hwang, Jun-Ha; Moon, Sung Ah; Lee, Cham Han; Byun, Mi Ran; Kim, A Rum; Sung, Mi Kyung; Park, Hyun-Jin; Hwang, Eun Sook; Sung, Sang Hyun; Hong, Jeong-Ho

    2012-06-15

    Obesity is a major health problem worldwide and can increase the risk for several chronic diseases, including diabetes and cardiovascular disease. In this study, we screened small compounds isolated from natural products for the development of an anti-obesity drug. Among them, idesolide, a spiro compound isolated from the fruits of Idesia polycarpa Maxim, showed a significant suppression of the adipogenic differentiation in mesenchymal cells, as indicated by the decrease in fat droplets and expression of adipogenic marker genes such as aP2 and adiponectin. Idesolide inhibits the PPARγ-mediated gene transcription in a dose-dependent manner, revealed by luciferase reporter gene assay. During adipogenic differentiation, idesolide inhibits nitric oxide production through the suppression of iNOS expression, and the increased adipogenic differentiation by arginine, the substrate for NOS, is significantly inhibited by idesolide, suggesting that the inhibition of nitric oxide production plays a major role in idesolide-induced adipogenic suppression. Taken together, the results reveal that idesolide has anti-adipogenic activity and highlight its potential in the prevention and treatment of obesity.

  5. Factors Associated with Nitric Oxide-mediated β2 Integrin Inhibition of Neutrophils*

    PubMed Central

    Bhopale, Veena M.; Yang, Ming; Yu, Kevin; Thom, Stephen R.

    2015-01-01

    This investigation explored the mechanism for inhibition of β2 integrin adhesion molecules when neutrophils are exposed to nitric oxide (•NO). Roles for specific proteins were elucidated using chemical inhibitors, depletion with small inhibitory RNA, and cells from knock-out mice. Optimal inhibition occurs with exposures to a •NO flux of ∼28 nmol/min for 2 min or more, which sets up an autocatalytic cascade triggered by activating type 2 nitric-oxide synthase (NOS-2) and NADPH oxidase (NOX). Integrin inhibition does not occur with neutrophils exposed to a NOX inhibitor (Nox2ds), a NOS-2 inhibitor (1400W), or with cells from mice lacking NOS-2 or the gp91phox component of NOX. Reactive species cause S-nitrosylation of cytosolic actin that enhances actin polymerization. Protein cross-linking and actin filament formation assays indicate that increased polymerization occurs because of associations involving vasodilator-stimulated phosphoprotein, focal adhesion kinase, and protein-disulfide isomerase in proximity to actin filaments. These effects were inhibited in cells exposed to ultraviolet light which photo-reverses S-nitrosylated cysteine residues and by co-incubations with cytochalasin D. The autocatalytic cycle can be arrested by protein kinase G activated with 8-bromo-cyclic GMP and by a high •NO flux (∼112 nmol/min) that inactivates NOX. PMID:26032418

  6. Modeling Species Inhibition of NO Oxidation in Urea-SCR Catalysts for Diesel Engine NOx Control

    SciTech Connect

    Devarakonda, Maruthi N.; Tonkyn, Russell G.; Tran, Diana N.; Lee, Jong H.; Herling, Darrell R.

    2011-04-20

    Urea-selective catalytic reduction (SCR) catalysts are regarded as the leading NOx aftertreatment technology to meet the 2010 NOx emission standards for on-highway vehicles running on heavy-duty diesel engines. However, issues such as low NOx conversion at low temperature conditions still exist due to various factors, including incomplete urea thermolysis, inhibition of SCR reactions by hydrocarbons and H2O. We have observed a noticeable reduction in the standard SCR reaction efficiency at low temperature with increasing water content. We observed a similar effect when hydrocarbons are present in the stream. This effect is absent under fast SCR conditions where NO ~ NO2 in the feed gas. As a first step in understanding the effects of such inhibition on SCR reaction steps, kinetic models that predict the inhibition behavior of H2O and hydrocarbons on NO oxidation are presented in the paper. A one-dimensional SCR model was developed based on conservation of species equations and was coded as a C-language S-function and implemented in Matlab/Simulink environment. NO oxidation and NO2 dissociation kinetics were defined as a function of the respective adsorbate’s storage in the Fe-zeolite SCR catalyst. The corresponding kinetic models were then validated on temperature ramp tests that showed good match with the test data. Such inhibition models will improve the accuracy of model based control design for integrated DPF-SCR aftertreatment systems.

  7. Di (2-ethylhexyl) phthalate inhibits growth of ovarian antral follicles through an oxidative stress pathway

    PubMed Central

    Wang, Wei; Craig, Zelieann R.; Basavarajappa, Mallikarjuna S.; Gupta, Rupesh; Flaws, Jodi A.

    2011-01-01

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 32–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. PMID:22155089

  8. Differential inhibition of CYP1-catalyzed regioselective hydroxylation of estradiol by berberine and its oxidative metabolites.

    PubMed

    Chang, Yu-Ping; Huang, Chiung-Chiao; Shen, Chien-Chang; Tsai, Keng-Chang; Ueng, Yune-Fang

    2015-10-01

    Berberine is a pharmacologically active alkaloid present in widely used medicinal plants, such as Coptis chinensis (Huang-Lian). The hormone estradiol is oxidized by cytochrome P450 (CYP) 1B1 to primarily form the genotoxic metabolite 4-hydroxyestradiol, whereas CYP1A1 and CYP1A2 predominantly generate 2-hydroxyestradiol. To illustrate the effect of berberine on the regioselective oxidation of estradiol, effects of berberine and its metabolites on CYP1 activities were studied. Among CYP1s, CYP1B1.1, 1.3 (L432V), and 1.4 (N453S)-catalyzed 4-hydroxylation were preferentially inhibited by berberine. Differing from the competitive inhibition of CYP1B1.1 and 1.3, N453S substitution in CYP1B1 allowed a non-competitive or mixed-type pattern. An N228T in CYP1B1 highly decreased its activity and preference to 4-hydroxylation. A reverse mutation of T223N in CYP1A2 retained its 2-hydroxylation preference, but enhanced its inhibition susceptibility to berberine. Compared with berberine, metabolites demethyleneberberine and thalifendine caused weaker inhibition of CYP1A1 and CYP1B1 activities. Unexpectedly, thalifendine was more potent than berberine in the inhibition of CYP1A2, in which case an enhanced interaction through polar hydrogen-π bond was predicted from the docking analysis. These results demonstrate that berberine preferentially inhibits the estradiol 4-hydroxylation activity of CYP1B1 variants, suggesting that 4-hydroxyestradiol-mediated toxicity might be reduced by berberine, especially in tissues/tumors highly expressing CYP1B1.

  9. Inhibition of plasmonically enhanced interdot energy transfer in quantum dot solids via photo-oxidation

    SciTech Connect

    Sadeghi, S. M.; Nejat, A.; West, R. G.

    2012-11-15

    We studied the impact of photophysical and photochemical processes on the interdot Forster energy transfer in monodisperse CdSe/ZnS quantum dot solids. For this, we investigated emission spectra of CdSe/ZnS quantum dot solids in the vicinity of gold metallic nanoparticles coated with chromium oxide. The metallic nanoparticles were used to enhance the rate of the energy transfer between the quantum dots, while the chromium oxide coating led to significant increase of their photo-oxidation rates. Our results showed that irradiation of such solids with a laser beam can lead to unique spectral changes, including narrowing and blue shift. We investigate these effects in terms of inhibition of the plasmonically enhanced interdot energy transfer between quantum dots via the chromium-oxide accelerated photo-oxidation process. We demonstrate this considering energy-dependent rate of the interdot energy transfer process, plasmonic effects, and the way photo-oxidation enhances non-radiative decay rates of quantum dots with different sizes.

  10. Matrix metalloproteinase inhibition reduces oxidative stress associated with cerebral amyloid angiopathy in vivo in transgenic mice.

    PubMed

    Garcia-Alloza, Monica; Prada, Claudia; Lattarulo, Carli; Fine, Sara; Borrelli, Laura A; Betensky, Rebecca; Greenberg, Steven M; Frosch, Matthew P; Bacskai, Brian J

    2009-06-01

    Cerebral amyloid angiopathy (CAA), characterized by extracellular beta-amyloid peptide (Abeta) deposits in vessel walls, is present in the majority of cases of Alzheimer's disease and is a major cause of hemorrhagic stroke. Although the molecular pathways activated by vascular Abeta are poorly understood, extracellular matrix metalloproteinases (MMP) and Abeta-induced oxidative stress appear to play important roles. We adapted fluorogenic assays for MMP activity and reactive oxygen species generation for use in vivo. Using multiphoton microscopy in APPswe/PS1dE9 and Tg-2576 transgenic mice, we observed strong associations between MMP activation, oxidative stress, and CAA deposition in leptomeningeal vessels. Antioxidant treatment with alpha-phenyl-N-tert-butyl-nitrone reduced oxidative stress associated with CAA (approximately 50% reduction) without affecting MMP activation. Conversely, a selection of agents that inhibit MMP by different mechanisms of action, including minocycline, simvastatin, and GM6001, reduced not only CAA-associated MMP activation (approximately 30-40% reduction) but also oxidative stress (approximately 40% reduction). The inhibitors of MMP did not have direct antioxidant effects. Treatment of animals with alpha-phenyl-N-tert-butyl-nitrone or minocycline did not have a significant effect on CAA progression rates. These data suggest a close association between Abeta-related MMP activation and oxidative stress in vivo and raise the possibility that treatment with MMP inhibitors may have beneficial effects by indirectly reducing the oxidative stress associated with CAA.

  11. Inhibition of protein and lipid oxidation in liposomes by berry phenolics.

    PubMed

    Viljanen, Kaarina; Kylli, Petri; Kivikari, Riitta; Heinonen, Marina

    2004-12-01

    The antioxidant activity of berry phenolics (at concentrations of 1.4, 4.2, and 8.4 mug of purified extracts/mL of liposome sample) such as anthocyanins, ellagitannins, and proanthocyanidins from raspberry (Rubus idaeus), bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), and black currant (Ribes nigrum) was investigated in a lactalbumin-liposome system. The extent of protein oxidation was measured by determining the loss of tryptophan fluorescence and formation of protein carbonyl compounds and that of lipid oxidation by conjugated diene hydroperoxides and hexanal analyses. The antioxidant protection toward lipid oxidation was best provided by lingonberry and bilberry phenolics followed by black currant and raspberry phenolics. Bilberry and raspberry phenolics exhibited the best overall antioxidant activity toward protein oxidation. Proanthocyanidins, especially the dimeric and trimeric forms, in lingonberries were among the most active phenolic constituents toward both lipid and protein oxidation. In bilberries and black currants, anthocyanins contributed the most to the antioxidant effect by inhibiting the formation of both hexanal and protein carbonyls. In raspberries, ellagitannins were responsible for the antioxidant activity. While the antioxidant effect of berry proanthocyanidins and anthocyanins was dose-dependent, ellagitannins appeared to be equally active at all concentrations. In conclusion, berries are rich in monomeric and polymeric phenolic compounds providing protection toward both lipid and protein oxidation.

  12. Bismuth oxide aqueous colloidal nanoparticles inhibit Candida albicans growth and biofilm formation.

    PubMed

    Hernandez-Delgadillo, Rene; Velasco-Arias, Donaji; Martinez-Sanmiguel, Juan Jose; Diaz, David; Zumeta-Dube, Inti; Arevalo-Niño, Katiushka; Cabral-Romero, Claudio

    2013-01-01

    Multiresistance among microorganisms to common antimicrobials has become one of the most significant concerns in modern medicine. Nanomaterials are a new alternative to successfully treat the multiresistant microorganisms. Nanostructured materials are used in many fields, including biological sciences and medicine. Recently, it was demonstrated that the bactericidal activity of zero-valent bismuth colloidal nanoparticles inhibited the growth of Streptococcus mutans; however the antimycotic potential of bismuth nanostructured derivatives has not yet been studied. The main objective of this investigation was to analyze the fungicidal activity of bismuth oxide nanoparticles against Candida albicans, and their antibiofilm capabilities. Our results showed that aqueous colloidal bismuth oxide nanoparticles displayed antimicrobial activity against C. albicans growth (reducing colony size by 85%) and a complete inhibition of biofilm formation. These results are better than those obtained with chlorhexidine, nystatin, and terbinafine, the most effective oral antiseptic and commercial antifungal agents. In this work, we also compared the antimycotic activities of bulk bismuth oxide and bismuth nitrate, the precursor metallic salt. These results suggest that bismuth oxide colloidal nanoparticles could be a very interesting candidate as a fungicidal agent to be incorporated into an oral antiseptic. Additionally, we determined the minimum inhibitory concentration for the synthesized aqueous colloidal Bi2O3 nanoparticles.

  13. Terminalia bellirica Extract Inhibits Low-Density Lipoprotein Oxidation and Macrophage Inflammatory Response in Vitro

    PubMed Central

    Tanaka, Miori; Kishimoto, Yoshimi; Saita, Emi; Suzuki-Sugihara, Norie; Kamiya, Tomoyasu; Taguchi, Chie; Iida, Kaoruko; Kondo, Kazuo

    2016-01-01

    The deciduous tree Terminalia bellirica found in Southeast Asia is extensively used in traditional Indian Ayurvedic medicine for the treatment of hypertension, rheumatism, and diabetes. The anti-atherogenic effect of Terminalia bellirica fruit has not been fully elucidated. Here, we investigated the effect of Terminalia bellirica extract (TBE) on low-density lipoprotein (LDL) oxidation and inflammation in macrophages. TBE showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (EC50: 7.2 ± 1.2 μg/mL) and 15-lipoxygenase inhibitory activity. TBE also significantly inhibited free radical-induced LDL oxidation compared to the solvent control in vitro. In THP-1 macrophages, TBE treatment resulted in significant decreases of the mRNA expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and lectin-like oxidized LDL receptor-1 (LOX-1). TBE also reduced matrix metalloproteinase (MMP)-9 secretion and intracellular reactive oxygen species (ROS) production in THP-1 macrophages. These results show that TBE has the inhibitory effects on LDL oxidation and macrophage inflammatory response in vitro, suggesting that its in vivo use might inhibit atherosclerosis plaque progression. PMID:27314393

  14. Bismuth oxide aqueous colloidal nanoparticles inhibit Candida albicans growth and biofilm formation

    PubMed Central

    Hernandez-Delgadillo, Rene; Velasco-Arias, Donaji; Martinez-Sanmiguel, Juan Jose; Diaz, David; Zumeta-Dube, Inti; Arevalo-Niño, Katiushka; Cabral-Romero, Claudio

    2013-01-01

    Multiresistance among microorganisms to common antimicrobials has become one of the most significant concerns in modern medicine. Nanomaterials are a new alternative to successfully treat the multiresistant microorganisms. Nanostructured materials are used in many fields, including biological sciences and medicine. Recently, it was demonstrated that the bactericidal activity of zero-valent bismuth colloidal nanoparticles inhibited the growth of Streptococcus mutans; however the antimycotic potential of bismuth nanostructured derivatives has not yet been studied. The main objective of this investigation was to analyze the fungicidal activity of bismuth oxide nanoparticles against Candida albicans, and their antibiofilm capabilities. Our results showed that aqueous colloidal bismuth oxide nanoparticles displayed antimicrobial activity against C. albicans growth (reducing colony size by 85%) and a complete inhibition of biofilm formation. These results are better than those obtained with chlorhexidine, nystatin, and terbinafine, the most effective oral antiseptic and commercial antifungal agents. In this work, we also compared the antimycotic activities of bulk bismuth oxide and bismuth nitrate, the precursor metallic salt. These results suggest that bismuth oxide colloidal nanoparticles could be a very interesting candidate as a fungicidal agent to be incorporated into an oral antiseptic. Additionally, we determined the minimum inhibitory concentration for the synthesized aqueous colloidal Bi2O3 nanoparticles. PMID:23637533

  15. Effect of chronic renal medullary nitric oxide inhibition on blood pressure.

    PubMed

    Mattson, D L; Lu, S; Nakanishi, K; Papanek, P E; Cowley, A W

    1994-05-01

    The effects of chronic nitric oxide inhibition in the renal medulla on renal cortical and medullary blood flow, sodium balance, and blood pressure were evaluated in conscious uninephrectomized Sprague-Dawley rats. During a 5-day renal medullary interstitial infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 120 micrograms/h) in saline (0.5 ml/min), renal medullary blood flow was selectively decreased by 30% after 2 h and was maintained at that level for the entire infusion. The decrease in medullary blood flow was associated with sodium retention and increased blood pressure. After the cessation of L-NAME infusion, medullary blood flow returned to control, and the sodium balance became negative as blood pressure returned to baseline. These data indicate that renal medullary nitric oxide plays an important role in the regulation of renal blood flow, sodium excretion, and blood pressure.

  16. Inhibition of bacterial oxidation of ferrous iron by lead nitrate in sulfate-rich systems

    USGS Publications Warehouse

    Wang, Hongmei; Gong, Linfeng; Cravotta, Charles A.; Yang, Xiaofen; Tuovinen, Olli H.; Dong, Hailiang; Fu, Xiang

    2013-01-01

    Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO3)2 was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0–24.2 mM Pb(II) added as Pb(NO3)2. Anglesite (PbSO4) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe3(SO4)2(OH)6) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9–17.6 μM regardless of the concentrations of Pb(NO3)2 added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO3)2 addition even when anglesite was removed before inoculation. Experiments with 0–48 mM KNO3 demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO3)2 addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans.

  17. Inhibition of bacterial oxidation of ferrous iron by lead nitrate in sulfate-rich systems.

    PubMed

    Wang, Hongmei; Gong, Linfeng; Cravotta, Charles A; Yang, Xiaofen; Tuovinen, Olli H; Dong, Hailiang; Fu, Xiang

    2013-01-15

    Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO(3))(2) was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0-24.2 mM Pb(II) added as Pb(NO(3))(2). Anglesite (PbSO(4)) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe(3)(SO(4))(2)(OH)(6)) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9-17.6 μM regardless of the concentrations of Pb(NO(3))(2) added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO(3))(2) addition even when anglesite was removed before inoculation. Experiments with 0-48 mM KNO(3) demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO(3))(2) addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans.

  18. Inhibition of phenol on the rates of ammonia oxidation by Nitrosomonas europaea grown under batch, continuous fed, and biofilm conditions.

    PubMed

    Lauchnor, Ellen G; Semprini, Lewis

    2013-09-01

    Ammonia oxidation by Nitrosomonas europaea, an ammonia oxidizing bacterium prevalent in wastewater treatment, is inhibited in the presence of phenol, due to interaction of the phenol with the ammonia monooxygenase enzyme. Suspended cells of N. europaea were cultured in batch reactors and continuous flow reactors at dilution rates of 0.01-0.2 d(-1). The rate of ammonia oxidation in the continuous cultures correlated to the dilution rate in the reactor. The batch and continuous cultures were exposed to 20 μM phenol and ammonia oxidation activity was measured by specific oxygen uptake rates (SOURs). Inhibition of NH3 oxidation by 20 μM phenol ranged from a 77% reduction of SOUR observed with suspended cells harvested during exponential growth, to 26% in biofilms. The extent of inhibition was correlated with ammonia oxidation rates in both suspended and biofilm cells, with greater percent inhibition observed with higher initial rates of NH3 oxidation. In biofilm grown cells, an increase in activity and phenol inhibition were both observed upon dispersing the biofilm cells into fresh, liquid medium. Under higher oxygen tension, an increase in the NO2(-) production of the biofilms was observed and biofilms were more susceptible to phenol inhibition. Dissolved oxygen microsensor measurements showed oxygen limited conditions existed in the biofilms. The ammonia oxidation rate was much lower in biofilms, which were less inhibited during phenol exposure. The results clearly indicate in both suspended and attached cells of N. europaea that a higher extent of phenol inhibition is positively correlated with a higher rate of NH3 oxidation (enzyme turnover).

  19. Membrane hyperpolarization during human sperm capacitation

    PubMed Central

    López-González, I.; Torres-Rodríguez, P.; Sánchez-Carranza, O.; Solís-López, A.; Santi, C.M.; Darszon, A.; Treviño, C.L.

    2014-01-01

    Sperm capacitation is a complex and indispensable physiological process that spermatozoa must undergo in order to acquire fertilization capability. Spermatozoa from several mammalian species, including mice, exhibit a capacitation-associated plasma membrane hyperpolarization, which is necessary for the acrosome reaction to occur. Despite its importance, this hyperpolarization event has not been adequately examined in human sperm. In this report we used flow cytometry to show that a subpopulation of human sperm indeed undergo a plasma membrane hyperpolarization upon in vitro capacitation. This hyperpolarization correlated with two other well-characterized capacitation parameters, namely an increase in intracellular pH and Ca2+ concentration, measured also by flow cytometry. We found that sperm membrane hyperpolarization was completely abolished in the presence of a high external K+ concentration (60 mM), indicating the participation of K+ channels. In order to identify, which of the potential K+ channels were involved in this hyperpolarization, we used different K+ channel inhibitors including charybdotoxin, slotoxin and iberiotoxin (which target Slo1) and clofilium (a more specific blocker for Slo3). All these K+ channel antagonists inhibited membrane hyperpolarization to a similar extent, suggesting that both members of the Slo family may potentially participate. Two very recent papers recorded K+ currents in human sperm electrophysiologically, with some contradictory results. In the present work, we show through immunoblotting that Slo3 channels are present in the human sperm membrane. In addition, we found that human Slo3 channels expressed in CHO cells were sensitive to clofilium (50 μM). Considered altogether, our data indicate that Slo1 and Slo3 could share the preponderant role in the capacitation-associated hyperpolarization of human sperm in contrast to what has been previously reported for mouse sperm, where Slo3 channels are the main contributors to the

  20. The monocyte locomotion inhibitory factor produced by Entamoeba histolytica inhibits induced nitric oxide production in human leukocytes.

    PubMed

    Rico, G; Leandro, E; Rojas, S; Giménez, J A; Kretschmer, R R

    2003-07-01

    The monocyte locomotion inhibitory factor, an anti-inflammatory pentapeptide produced by Entamoeba histolytica, inhibits the in vitro production of nitric oxide induced by cytokines (INF-gamma, TNF-alpha) or PMA in human leukocytes. This can be added to the other previously reported functional effects of this factor, such as the inhibition of monocyte locomotion and the synthesis of reactive oxygen intermediates in both monocytes and neutrophils. The decreased nitric oxide production may interfere with the killing of amebas by neutrophils in the early invasive stages of amebiasis, when oxidative mechanisms are used [reactive oxygen and nitrogen intermediates either individually or synergistically via peroxynitrite (ONOO(-))], and in the advanced stages, when both non-oxidative and oxidative (including nitric oxide) mechanisms are employed by macrophages. Diminished nitric oxide production by leukocytes may also contribute to the paucity of late inflammatory components in amebic abscess of the liver and other amebic lesions.

  1. Inhibition of ROMK channels by low extracellular K+ and oxidative stress

    PubMed Central

    Frindt, Gustavo; Li, Hui; Sackin, Henry

    2013-01-01

    We tested the hypothesis that low luminal K+ inhibits the activity of ROMK channels in the rat cortical collecting duct. Whole-cell voltage-clamp measurements of the component of outward K+ current inhibited by the bee toxin Tertiapin-Q (ISK) showed that reducing the bath concentration ([K+]o) to 1 mM resulted in a decline of current over 2 min compared with that observed at 10 mM [K+]o. However, maintaining tubules in 1 mM [K+]o without establishing whole-cell clamp conditions did not affect ISK. The [K+]o-dependent decline was not prevented by increasing cytoplasmic-side pH or by inhibition of phosphatase activity. It was, however, abolished by the inclusion of 0.5 mM DTT in the pipette solution to prevent oxidation of the intracellular environment. Conversely, treatment of intact tubules with the oxidant H2O2 (100 μM) decreased ISK in a [K+]o-dependent manner. Treatment of the tubules with the phospholipase C inhibitor U73122 prevented the effect of low [K+]o, suggesting the involvement of this enzyme in the process. We examined these effects further using Xenopus oocytes expressing ROMK2 channels. A 50-min exposure to the permeant oxidizing agent tert-butyl hydroperoxide (t-BHP; 500 μM) did not affect outward K+ currents with [K+]o = 10 mM but reduced currents by 50% with [K+]o = 1 mM and by 75% with [K+]o = 0.1 mM. Pretreatment of the oocytes with U73122 prevented the effects of t-BHP. Under conditions of low dietary K intake, K+ secretion by distal nephron segments may be suppressed by a combination of low luminal [K+]o and oxidative stress. PMID:23678039

  2. Improved Capacitive Liquid Sensor

    NASA Technical Reports Server (NTRS)

    Waldman, Francis A.

    1992-01-01

    Improved capacitive sensor used to detect presence and/or measure thickness of layer of liquid. Electrical impedance or admittance of sensor measured at prescribed frequency, and thickness of liquid inferred from predetermined theoretical or experimental relationship between impedance and thickness. Sensor is basically a three-terminal device. Features interdigitated driving and sensing electrodes and peripheral coplanar ground electrode that reduces parasitic effects. Patent-pending because first to utilize ground plane as "shunting" electrode. System less expensive than infrared, microwave, or refractive-index systems. Sensor successfully evaluated in commercial production plants to characterize emulsions, slurries, and solutions.

  3. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1983-07-15

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  4. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1985-11-12

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label. 5 figs.

  5. Capacitive label reader

    DOEpatents

    Arlowe, H. Duane

    1985-01-01

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  6. Rapid assessment of singlet oxygen-induced plasma lipid oxidation and its inhibition by antioxidants with diphenyl-1-pyrenylphosphine (DPPP).

    PubMed

    Morita, Mayuko; Naito, Yuji; Yoshikawa, Toshikazu; Niki, Etsuo

    2016-01-01

    Recent studies suggesting the involvement of singlet oxygen in the pathogenesis of multiple diseases have attracted renewed attention to lipid oxidation mediated by singlet oxygen. Although the rate constants for singlet oxygen quenching by antioxidants have been measured extensively, the inhibition of lipid oxidation mediated by singlet oxygen has received relatively less attention, partly because a convenient method for measuring the rate of lipid oxidation is not available. The objective of this study was to develop a convenient method to measure plasma lipid oxidation mediated by singlet oxygen which may be applied to a rapid assessment of the antioxidant capacity to inhibit this oxidation using a conventional microplate reader. Singlet oxygen was produced from naphthalene endoperoxide, and lipid hydroperoxide production was followed by using diphenyl-1-pyrenylphosphine (DPPP). Non-fluorescent DPPP reacts stoichiometrically with lipid hydroperoxides to give highly fluorescent DPPP oxide. It was found that plasma oxidation by singlet oxygen increased the fluorescence intensity of DPPP oxide, which was suppressed by antioxidants. Fucoxanthin suppressed the oxidation more efficiently than β-carotene and α-tocopherol, while ascorbic acid and Trolox were not effective. The present method may be useful for monitoring lipid oxidation and also for rapid screening of the capacity of dietary antioxidants and natural products to inhibit lipid oxidation in a biologically relevant system.

  7. Inhibition of Adenylyl Cyclase Type 5 Increases Longevity and Healthful Aging through Oxidative Stress Protection

    PubMed Central

    Vatner, Stephen F.; Pachon, Ronald E.; Vatner, Dorothy E.

    2015-01-01

    Mice with disruption of adenylyl cyclase type 5 (AC5 knockout, KO) live a third longer than littermates. The mechanism, in part, involves the MEK/ERK pathway, which in turn is related to protection against oxidative stress. The AC5 KO model also protects against diabetes, obesity, and the cardiomyopathy induced by aging, diabetes, and cardiac stress and also demonstrates improved exercise capacity. All of these salutary features are also mediated, in part, by oxidative stress protection. For example, chronic beta adrenergic receptor stimulation induced cardiomyopathy was rescued by AC5 KO. Conversely, in AC5 transgenic (Tg) mice, where AC5 is overexpressed in the heart, the cardiomyopathy was exacerbated and was rescued by enhancing oxidative stress resistance. Thus, the AC5 KO model, which resists oxidative stress, is uniquely designed for clinical translation, since it not only increases longevity and exercise, but also protects against diabetes, obesity, and cardiomyopathy. Importantly, inhibition of AC5's action to prolong longevity and enhance healthful aging, as well as its mechanism through resistance to oxidative stress, is unique among all of the nine AC isoforms. PMID:25945149

  8. Use of Walnut Shell Powder to Inhibit Expression of Fe2+-Oxidizing Genes of Acidithiobacillus Ferrooxidans

    PubMed Central

    Li, Yuhui; Liu, Yehao; Tan, Huifang; Zhang, Yifeng; Yue, Mei

    2016-01-01

    Acidithiobacillus ferrooxidans is a Gram-negative bacterium that obtains energy by oxidizing Fe2+ or reduced sulfur compounds. This bacterium contributes to the formation of acid mine drainage (AMD). This study determined whether walnut shell powder inhibits the growth of A. ferrooxidans. First, the effects of walnut shell powder on Fe2+ oxidization and H+ production were evaluated. Second, the chemical constituents of walnut shell were isolated to determine the active ingredient(s). Third, the expression of Fe2+-oxidizing genes and rus operon genes was investigated using real-time polymerase chain reaction. Finally, growth curves were plotted, and a bioleaching experiment was performed to confirm the active ingredient(s) in walnut shells. The results indicated that both walnut shell powder and the phenolic fraction exert high inhibitory effects on Fe2+ oxidation and H+ production by A. ferrooxidans cultured in standard 9K medium. The phenolic components exert their inhibitory effects by down-regulating the expression of Fe2+-oxidizing genes and rus operon genes, which significantly decreased the growth of A. ferrooxidans. This study revealed walnut shell powder to be a promising substance for controlling AMD. PMID:27144574

  9. Plant-Derived Phenolics Inhibit the Accrual of Structurally Characterised Protein and Lipid Oxidative Modifications

    PubMed Central

    Naudí, Alba; Romero, Maria-Paz; Cassanyé, Anna; Serrano, José C. E.; Arola, Lluis; Valls, Josep; Bellmunt, Maria Josep; Prat, Joan; Pamplona, Reinald; Portero-Otin, Manuel; Motilva, Maria-José

    2012-01-01

    Epidemiological data suggest that plant-derived phenolics beneficial effects include an inhibition of LDL oxidation. After applying a screening method based on 2,4-dinitrophenyl hydrazine- protein carbonyl reaction to 21 different plant-derived phenolic acids, we selected the most antioxidant ones. Their effect was assessed in 5 different oxidation systems, as well as in other model proteins. Mass-spectrometry was then used, evidencing a heterogeneous effect on the accumulation of the structurally characterized protein carbonyl glutamic and aminoadipic semialdehydes as well as for malondialdehyde-lysine in LDL apoprotein. After TOF based lipidomics, we identified the most abundant differential lipids in Cu++-incubated LDL as 1-palmitoyllysophosphatidylcholine and 1-stearoyl-sn-glycero-3-phosphocholine. Most of selected phenolic compounds prevented the accumulation of those phospholipids and the cellular impairment induced by oxidized LDL. Finally, to validate these effects in vivo, we evaluated the effect of the intake of a phenolic-enriched extract in plasma protein and lipid modifications in a well-established model of atherosclerosis (diet-induced hypercholesterolemia in hamsters). This showed that a dietary supplement with a phenolic-enriched extract diminished plasma protein oxidative and lipid damage. Globally, these data show structural basis of antioxidant properties of plant-derived phenolic acids in protein oxidation that may be relevant for the health-promoting effects of its dietary intake. PMID:22952663

  10. Effect of Extra-Framework Cations of LTL Nanozeolites to Inhibit Oil Oxidation

    NASA Astrophysics Data System (ADS)

    Tan, Kok-Hou; Cham, Hooi-Ying; Awala, Hussein; Ling, Tau Chuan; Mukti, Rino R.; Wong, Ka-Lun; Mintova, Svetlana; Ng, Eng-Poh

    2015-06-01

    Lubricant oils take significant part in current health and environmental considerations since they are an integral and indispensable component of modern technology. Antioxidants are probably the most important additives used in oils because oxidative deterioration plays a major role in oil degradation. Zeolite nanoparticles (NPs) have been proven as another option as green antioxidants in oil formulation. The anti-oxidative behavior of zeolite NPs is obvious; however, the phenomenon is still under investigation. Herein, a study of the effect of extra-framework cations stabilized on Linde Type L (LTL) zeolite NPs (ca. 20 nm) on inhibition of oxidation in palm oil-based lubricant oil is reported. Hydrophilic LTL zeolites with a Si/Al ratio of 3.2 containing four different inorganic cations (Li+, Na+, K+, Ca2+) were applied. The oxidation of the lubricant oil was followed by visual observation, colorimetry, fourier transform infrared (FTIR) spectroscopy, 1H NMR spectroscopy, total acid number (TAN), and rheology analyses. The effect of extra-framework cations to slow down the rate of oil oxidation and to control the viscosity of oil is demonstrated. The degradation rate of the lubricant oil samples is decreased considerably as the polarizability of cation is increased with the presence of zeolite NPs. More importantly, the microporous zeolite NPs have a great influence in halting the steps that lead to the polymerization of the oils and thus increasing the lifetime of oils.

  11. Corrosion inhibition properties of graphene oxide on mild steel in 3.5% NaCl

    NASA Astrophysics Data System (ADS)

    Anandh Senthilvasan, Prem; Rangarajan, Murali

    2016-09-01

    In this work the corrosion inhibition of mild steel in 3.5% Sodium chloride (NaCl) solution at ambient conditions by Graphene Oxide (GO) has been studied. Graphene oxide was prepared by Modified Hummers Method and characterized by Fourier Transform Infrared spectroscopy (FTIR), UV-Visible spectroscopy (UV-Vis), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Thermo-Gravimetric Analysis (TGA). The electrochemical corrosion behaviour of mild steel has been studied in the absence and presence of GO coatings by Tafel polarization and impedance analyses. The modified electrode has 44.8mV potential shift in the cathodic direction and reduction in current by 41.9 μA (61%). This indicates the strong protection offered by graphene oxide film. The obtained impedance spectra also clearly show that the charge transfer resistance of graphene oxide film is much higher than that of the uncoated steel electrode, demonstrating the strong protection offered by graphene oxide films for mild steel.

  12. An exactly solvable model for the graphene transistor in the quantum capacitance limit

    NASA Astrophysics Data System (ADS)

    Parrish, Kristen N.; Akinwande, Deji

    2012-07-01

    We explore the ultimate behavior of the graphene transistor in the quantum capacitance limit. The quantum capacitance formulation allows for an exactly solvable model, and the ideal assumptions provide an upper bound on performance, including peak currents of 1 mA/μm with mobilities as low as 2000 cm2/V s for channel length of 1 μm, as well as linearly increasing transconductance not observed in conventional transistors. A negative differential resistance is predicted under certain conditions, with a maximum peak-to-valley-current ratio of 4. Finally, the effects of oxide scaling are elucidated and the oxide capacitances required for quantum capacitance limited behavior are quantified.

  13. Reduced graphene oxide induces cytotoxicity and inhibits photosynthetic performance of the green alga Scenedesmus obliquus.

    PubMed

    Du, Shaoting; Zhang, Peng; Zhang, Ranran; Lu, Qi; Liu, Lin; Bao, Xiaowei; Liu, Huijun

    2016-12-01

    Increased use of graphene materials might ultimately lead to their release into the environment. However, only a few studies have investigated the impact of graphene-based materials on green plants. In this study, the impact of reduced graphene oxide (RGO) on the microalgae Scenedesmus obliquus was evaluated to determine its phytotoxicity. Treatment with RGO suppressed the growth of the microalgae. The 72-h IC50 values of RGO evaluated using the logistic and Gompertz models were 148 and 151 mg L(-1), respectively. RGO significantly inhibited Chl a and Chl a/b levels in the algal cells. Chlorophyll a fluorescence analysis showed that RGO significantly down-regulated photosystem II activity. The mechanism of how RGO inhibited algal growth and photosynthetic performance was determined by analyzing the alterations in ultrastructural morphology. RGO adhered to the algal cell surface as a semitranslucent coating. Cell wall damage and membrane integrity loss occurred in the treated cells. Moreover, nuclear chromatin clumping and starch grain number increase were noted. These changes might be attributed to the increase in malondialdehyde and reactive oxygen species levels, which might have exceeded the scavenging ability of antioxidant enzymes (including peroxidase and superoxide dismutase). RGO impaired the extra- and intra-cellular morphology and increased oxidative stress and thus inhibited algal growth and photosynthesis.

  14. Modeling Species Inhibition of NO oxidation in Urea-SCR Catalysts for Diesel Engine NOx Control

    SciTech Connect

    Devarakonda, Maruthi N.; Tonkyn, Russell G.; Tran, Diana N.; Lee, Jong H.; Herling, Darrell R.

    2010-09-15

    Urea-selective catalytic reduction (SCR) catalysts are regarded as the leading NOx aftertreatment technology to meet the 2010 NOx emission standards for on-highway vehicles running on heavy-duty diesel engines. However, issues such as low NOx conversion at low temperature conditions still exist due to various factors, including incomplete urea thermolysis, inhibition of SCR reactions by hydrocarbons and H2O. We have observed a noticeable reduction in the standard SCR reaction efficiency at low temperature with increasing water content. We observed a similar effect when hydrocarbons are present in the stream. This effect is absent under fast SCR conditions where NO ~ NO2 in the feed gas. As a first step in understanding the effects of such inhibition on SCR reaction steps, kinetic models that predict the inhibition behavior of H2O and hydrocarbons on NO oxidation are presented in the paper. A one-dimensional SCR model was developed based on conservation of species equations and was coded as a C-language S-function and implemented in Matlab/Simulink environment. NO oxidation and NO2 dissociation kinetics were defined as a function of the respective adsorbate’s storage in the SCR catalyst. The corresponding kinetic models were then validated on temperature ramp tests that showed good match with the test data.

  15. Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone-Induced Oxidative Damage in K562 Cells

    PubMed Central

    Cao, Meng; Yang, Wenwen; Sun, Fengmei; Xu, Cheng

    2016-01-01

    Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure. PMID:27656260

  16. Ostene, a New Alkylene Oxide Copolymer Bone Hemostatic Material, Does Not Inhibit Bone Healing

    PubMed Central

    Magyar, Clara E.; Aghaloo, Tara L.; Atti, Elisa; Tetradis, Sotirios

    2009-01-01

    OBJECTIVE In this study, we investigate the effects of a soft bone hemostatic wax comprised of water-soluble alkylene oxide copolymers (Ostene; Ceremed, Inc., Los Angeles, CA) on bone healing in a rat calvaria defect model. We compared the effects with a control (no hemostatic agent) and bone wax, an insoluble and nonresorbable material commonly used for bone hemostasis. METHODS Two bilateral 3-mm circular noncritical-sized defects were made in the calvariae of 30 rats. Alkylene oxide copolymer or bone wax was applied or no hemostatic material was used (control). After 3, 6, and 12 weeks, rats were sacrificed and the calvariae excised. Bone healing, expressed as fractional bone volume (± standard error of the mean), was measured by microcomputed tomography. RESULTS Immediate hemostasis was achieved equally with bone wax and alkylene oxide copolymer. Bone wax-filled defects remained unchanged at all time points with negligible healing observed. At 3 weeks, no evidence of alkylene oxide copolymer was observed at the application site, with fractional bone volume significantly greater than bone wax-treated defects (0.20 ± 0.03 versus 0.02 ± 0.01; P = 0.0003). At 6 and 12-weeks, alkylene oxide copolymer-treated defects continued to show significantly greater healing versus bone wax (0.18 ± 0.04 versus 0.05 ± 0.01 and 0.31 ± 0.04 versus 0.06 ± 0.02, respectively). At all time points, alkylene oxide copolymer-treated and control defects showed good healing with no significant difference. CONCLUSION Alkylene oxide copolymer is an effective hemostatic agent that does not inhibit osteogenesis or bone healing. PMID:18981846

  17. Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis.

    PubMed

    Giardino, I; Fard, A K; Hatchell, D L; Brownlee, M

    1998-07-01

    Aminoguanidine (AG) treatment, like nerve growth factor (NGF) treatment, prevents diabetes-induced apoptosis of retinal Müller cells in the rat eye, but the mechanism involved is unknown. In this study, the effects of preincubation with AG on oxidant-induced apoptosis, oxidant-induced intracellular reactive oxygen species (ROS) production, and lipid peroxidation were determined in rat retinal Müller cells and compared with the effects of NGF, a protein that protects neuronal cells from oxidative stress. The effect of AG on rabbit vitreous lipid peroxide levels was also determined. After exposure to increasing concentrations of H2O2, there was a corresponding increase in the percentage of apoptotic Müller cells. Preincubation with AG for 48 h completely inhibited oxidant-induced apoptosis in response to 10 micromol/l H2O2 (+AG 0 vs. 10 micromol/l, NS), and reduced the percentage of apoptotic cells in response to 50 micromol/l H2O2 by 50% (+AG vs. -AG, P < 0.01). Longer preincubation did not increase the antiapoptotic effect of AG. The effect of AG was dose-dependent. Similar results were obtained after preincubation with NGF. Both AG and NGF preincubation prevented the twofold increase in oxidant-induced lipid peroxides. The fivefold increase in oxidant-induced ROS production was decreased 100% by NGF, but only 61% by AG preincubation. The twofold increase in vitreous lipid peroxide level in diabetic rabbits was completely prevented by AG treatment. AG reduced H2O2-induced benzoate hydroxylation in a dose-dependent manner. Intracellular glutathione content was unchanged. These data demonstrate that AG can act as an antioxidant in vivo, quenching hydroxyl radicals and lipid peroxidation in cells and tissues and preventing oxidant-induced apoptosis.

  18. Programmable electronic synthesized capacitance

    NASA Technical Reports Server (NTRS)

    Kleinberg, Leonard L. (Inventor)

    1987-01-01

    A predetermined and variable synthesized capacitance which may be incorporated into the resonant portion of an electronic oscillator for the purpose of tuning the oscillator comprises a programmable operational amplifier circuit. The operational amplifier circuit has its output connected to its inverting input, in a follower configuration, by a network which is low impedance at the operational frequency of the circuit. The output of the operational amplifier is also connected to the noninverting input by a capacitor. The noninverting input appears as a synthesized capacitance which may be varied with a variation in gain-bandwidth product of the operational amplifier circuit. The gain-bandwidth product may, in turn, be varied with a variation in input set current with a digital to analog converter whose output is varied with a command word. The output impedance of the circuit may also be varied by the output set current. This circuit may provide very small ranges in oscillator frequency with relatively large control voltages unaffected by noise.

  19. Nitric oxide mediates low magnesium inhibition of osteoblast-like cell proliferation.

    PubMed

    Leidi, Marzia; Dellera, Federica; Mariotti, Massimo; Banfi, Giuseppe; Crapanzano, Calogero; Albisetti, Walter; Maier, Jeanette A M

    2012-10-01

    An adequate intake of magnesium (Mg) is important for bone cell activity and contributes to the prevention of osteoporosis. Because (a) Mg is mitogenic for osteoblasts and (b) reduction of osteoblast proliferation is detected in osteoporosis, we investigated the influence of different concentrations of extracellular Mg on osteoblast-like SaOS-2 cell behavior. We found that low Mg inhibited SaOS-2 cell proliferation by increasing the release of nitric oxide through the up-regulation of inducible nitric oxide synthase (iNOS). Indeed, both pharmacological inhibition with the iNOS inhibitor l-N(6)-(iminoethyl)-lysine-HCl and genetic silencing of iNOS by small interfering RNA restored the normal proliferation rate of the cells. Because a moderate induction of nitric oxide is sufficient to potentiate bone resorption and a relative deficiency in osteoblast proliferation can result in their inadequate activity, we conclude that maintaining Mg homeostasis is relevant to ensure osteoblast function and, therefore, to prevent osteoporosis.

  20. Influence of nitric oxide synthase inhibition on vasopressin and corticosterone secretion during water deprivation in rats.

    PubMed

    Mornagui, Bessem; Rezg, Raja; Grissa, Abir; Duvareille, Monique; Gharib, Claude; Kamoun, Abdelaziz; El-Fazaa, Saloua; Gharbi, Najoua

    2010-12-01

    Nitric oxide (NO) is a short-lived radical that functions as a neurotransmitter in the central nervous system and plays a physiological role in the regulation of hypothalamic-pituitary-adrenal axis and vasopressinergic axis. In the present study, we aimed to investigate the interaction between the generation of NO and vasopressin (AVP) and corticosterone release after 3 days of water deprivation in rats. Animals were previously treated with intraperitoneal (i.p.) saline or L-nitro-arginine methyl ester (L-NAME) injection. L-NAME is a nonspecific inhibitor of nitric oxide synthases. In control rats given i.p. saline or L-NAME, hypothalamic, pituitary, and plasma AVP levels and plasma corticosterone did not change from baseline levels (p>0.05). Three days of water deprivation increased significantly the corticosterone levels in plasma (p<0.01) and AVP levels in hypothalamus and plasma (p<0.01), but not in pituitary, which showed a significant decrease. These variations were concomitant with the elevation of nitrates/nitrates in plasma. L-NAME injection abolished significantly (p<0.01) the elevation of plasma corticosterone and hypothalamic AVP levels induced by water deprivation. These findings showed that in water-deprived rats, nitric oxide synthase inhibition by L-NAME inhibits corticosterone and vasopressin release, suggesting a potent stimulatory role of NO.

  1. Potent inhibition of macrophage migration inhibitory factor (MIF) by myeloperoxidase-dependent oxidation of epicatechins.

    PubMed

    Dickerhof, Nina; Magon, Nicholas J; Tyndall, Joel D A; Kettle, Anthony J; Hampton, Mark B

    2014-09-01

    MIF (macrophage migration inhibitory factor) plays a central role in the promotion and maintenance of the inflammatory response. It is implicated in a number of inflammatory diseases including sepsis, arthritis and colitis, and in diseases with an inflammatory component, such as atherosclerosis, diabetes and cancer. MIF has an unusual N-terminal proline with catalytic activity, and targeting of this residue by small-molecule inhibitors has been shown to interfere with the biological activity of MIF. The objective of the present study was to determine if MIF was susceptible to modification by epicatechins, a group of dietary flavonoids with known anti-inflammatory properties. Epicatechins are substrates for peroxidases including neutrophil-derived MPO (myeloperoxidase). In the present study we show that oxidation of the catechol moiety of epicatechins to an ο-quinone by MPO generates potent MIF inhibitors. Near complete inhibition of MIF by the MPO/H2O2/epicatechin system was achieved at equimolar concentrations of epicatechin and MIF, even in the presence of other MPO substrates. We have characterized the modification introduced by oxidized (-)-epicatechin on MIF by LC-MS (liquid chromatography MS) and found it to occur at the N-terminal proline. We propose that MIF inhibition by oxidized epicatechins contributes to the anti-inflammatory activity of these compounds.

  2. Inhibition of pyrite oxidation by surface coating agents: Batch and field studies

    NASA Astrophysics Data System (ADS)

    Choi, Jaeyoung; Do Gee, Eun; Yun, Hyun-Shik; Ram Lee, Woo; Park, Young-Tae

    2013-04-01

    The potential of several surface coating agents to inhibit the oxidation of metal sulfide minerals from Young-Dong coal mine and the Il-Gwang gold mine was examined by conducting laboratory scale batch experiments and field tests. Powdered pyrite as a standard sulfide mineral and rock samples from two mine outcrops were mixed with six coating agents (KH2PO4, MgO and KMnO4 as chemical agents, and apatite, cement and manganite as mineral agents) and incubated with oxidizing agents (H2O2 or NaClO). For the observed time period (8 days), Young-Dong coal mine samples exhibited the least sulfate (SO42-) production in the presence of KMnO4 (16%) or cement (4%) while, for Il-Gwang mine samples, the least SO42- production was observed in presence of KH2PO4 (8%) or cement (2%) compared to control. Field-scale pilot tests at the Il-Gwang site also showed that addition of KH2PO4 decreased SO42- production from 200 to 13 mg L-1 and it also reduced Cu and Mn from 8 and 3 mg L-1, respectively to <0.05 mg L-1 (below ICP-OES detection limits). The experimental results suggested that the use of surface coating agents is a promising alternative for sulfide oxidation inhibition at acid mine drainage sites.

  3. Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication.

    PubMed Central

    Croen, K D

    1993-01-01

    Nitric oxide (NO) has antimicrobial activity against a wide spectrum of infectious pathogens, but an antiviral effect has not been reported. The impact of NO, from endogenous and exogenous sources, on herpes simplex virus type 1 (HSV 1) replication was studied in vitro. HSV 1 replication in RAW 264.7 macrophages was reduced 1,806-fold in monolayers induced to make NO by activation with gamma IFN and LPS. A competitive and a noncompetitive inhibitor of nitric oxide synthetase substantially reduced the antiviral effect of activated RAW macrophages. S-nitroso-L-acetyl penicillamine (SNAP) is a donor of NO and was added to the media of infected monolayers to assess the antiviral properties of NO in the absence of gamma IFN and LPS. A single dose of S-nitroso-L-acetyl penicillamine 3 h after infection inhibited HSV 1 replication in Vero, HEp2, and RAW 264.7 cells in a dose-dependent manner. Neither virucidal nor cytocidal effects of NO were observed under conditions that inhibited HSV 1 replication. Nitric oxide had inhibitory effects, comparable to that of gamma IFN/LPS, on protein and DNA synthesis as well as on cell replication. This report demonstrates that, among its diverse properties, NO has an antiviral effect. PMID:8390481

  4. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    SciTech Connect

    Wang, Wei Craig, Zelieann R. Basavarajappa, Mallikarjuna S. Gupta, Rupesh K. Flaws, Jodi A.

    2012-01-15

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral

  5. Inhibition of nitric oxide-induced apoptosis by nicotine in oral epithelial cells.

    PubMed

    Banerjee, Abhijit G; Gopalakrishnan, Velliyur K; Vishwanatha, Jamboor K

    2007-11-01

    Development of oral cancer is clearly linked to the usage of smokeless tobacco. The molecular mechanisms involved in this process are however not well understood. Toward this goal, we investigated the effect of smokeless tobacco exposure on apoptosis of oral epithelial cells. Exposure of oral epithelial cells to smokeless tobacco extract (STE) induces apoptosis in a dose-dependent manner, until a threshold level of nicotine is achieved upon which apoptosis is inhibited. 1 mM of nicotine is able to inhibit apoptosis significantly induced by STE in these oral cells. Exposure of cells to nicotine alone has no effect on apoptosis, but nicotine inhibits apoptosis induced by other agents present in STE. In this study we show that, the anti-apoptotic action of nicotine is specifically associated with down-regulation of nitric oxide (NO) production. Using specific inducers of NO, we have demonstrated that inhibition of apoptosis by nicotine is through down-regulation of NO production. Further, we observed that nicotine clearly acts as a sink of NO radicals, shown using peroxynitrite generator (SIN-1) in conjunction or absence of radical scavengers. Nicotine thus causes most damage in transformed epithelial cells as depicted by accumulation of nitrotyrosine in a 3-NT ELISA assay. Inhibition of apoptosis is a hallmark in tumor progression and propels development of cancer. It may further result in functional loss of apoptotic effector mechanisms in the transformed cells. Thus, our data clearly indicates that inhibition of NO-induced apoptosis by nicotine may lead to tobacco-induced oral carcinogenesis, and implies careful development of modalities in tobacco cessation programs.

  6. Human astrocytes inhibit Cryptococcus neoformans growth by a nitric oxide-mediated mechanism

    PubMed Central

    1994-01-01

    Cryptococcus neoformans is an opportunistic fungus that causes life- threatening meningoencephalitis in 5-10% of patients with acquired immune deficiency syndrome. Cryptococcal meningoencephalitis is characterized by a lymphohistiocytic infiltrate, accumulation of encapsulated forms of C. neoformans, and varying degrees of glial reaction. Little is known about the contribution of endogenous central nervous system cells to the pathogenesis of cryptococcal infections. In this study, we investigated the role of astrocytes as potential effector cells against C. neoformans. Primary cultures of human fetal astrocytes, activated with interleukin 1 beta plus interferon gamma inhibited the growth of C. neoformans. The inhibition of C. neoformans growth was paralleled by production of nitrite, and reversed by the inhibitors of nitric oxide (NO.) synthase, NG-methyl-mono-arginine and NG-nitro-arginine methyl ester. The results suggest a novel function for human astrocytes in host defence and provide a precedent for the use of NO. as an antimicrobial effector molecule by human cells. PMID:8006595

  7. Chitinous materials inhibit nitric oxide production by activated RAW 264.7 macrophages.

    PubMed

    Hwang, S M; Chen, C Y; Chen, S S; Chen, J C

    2000-04-29

    Chitinous materials have been studied in wound healing and artificial skin substitutes for many years. Nitric oxide (NO) has been shown to contribute to cytotoxicity in cell proliferation during inflammation of wound healing. In this study, we examined the effect of chitin and its derivatives on NO production by activated RAW 264.7 macrophages. Chitin and chitosan showed a significantly inhibitory effect on NO production by the activated macrophages. Hexa-N-acetylchitohexaose and penta-N-acetylchitopentaose also inhibited NO production but with less potency. However, N-acetylchitotetraose, -triose, -biose, and monomer of chitin, N-acetylglucosamine and glucosamine had little effect on NO production by the activated cells. These results suggest that the promotive effect of chitinous material on wound healing be related, at least partly, to inhibit NO production by the activated macrophages.

  8. Inhibition of melanogenesis and oxidation by protocatechuic acid from Origanum vulgare (oregano).

    PubMed

    Chou, Tzung-Han; Ding, Hsiou-Yu; Lin, Rong-Jyh; Liang, Jing-Yao; Liang, Chia-Hua

    2010-11-29

    Antioxidant and antimelanogenesis activities of protocatechuic acid (1) from Origanum vulgare (oregano) were investigated. The antioxidative capacity of 1 was confirmed from its free-radical-scavenging activities, inhibition of lipid peroxidation, and suppression of reactive oxygen species in H(2)O(2)-induced BNLCL2 cells. The inhibition by 1 of tyrosinase and DOPA oxidase activity and melanin production was possibly related to the down-regulation of melanocortin-1 receptor, microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related proteins-2, and tyrosinase-related proteins-1 expression in α-melanocyte-stimulating hormone-induced B16 cells. After a gel containing 1 was applied to mice, the values of L* slightly increased, and a* and erythema-melanin levels of skin were reduced by comparing the values of untreated control groups, indicating 1 can reduce melanin production. These results suggest that 1 may act as an effective quencher of oxidative attackers with antimelanogenesis properties.

  9. Reactive Oxygen Species Mediated Bacterial Biofilm Inhibition via Zinc Oxide Nanoparticles and Their Statistical Determination

    PubMed Central

    Dwivedi, Sourabh; Wahab, Rizwan; Khan, Farheen; Mishra, Yogendra K.; Musarrat, Javed; Al-Khedhairy, Abdulaziz A.

    2014-01-01

    The formation of bacterial biofilm is a major challenge in clinical applications. The main aim of this study is to describe the synthesis, characterization and biocidal potential of zinc oxide nanoparticles (NPs) against bacterial strain Pseudomonas aeruginosa. These nanoparticles were synthesized via soft chemical solution process in a very short time and their structural properties have been investigated in detail by using X-ray diffraction and transmission electron microscopy measurements. In this work, the potential of synthesized ZnO-NPs (∼10–15 nm) has been assessed in-vitro inhibition of bacteria and the formation of their biofilms was observed using the tissue culture plate assays. The crystal violet staining on biofilm formation and its optical density revealed the effect on biofilm inhibition. The NPs at a concentration of 100 µg/mL significantly inhibited the growth of bacteria and biofilm formation. The biofilm inhibition by ZnO-NPs was also confirmed via bio-transmission electron microscopy (Bio-TEM). The Bio-TEM analysis of ZnO-NPs treated bacteria confirmed the deformation and damage of cells. The bacterial growth in presence of NPs concluded the bactericidal ability of NPs in a concentration dependent manner. It has been speculated that the antibacterial activity of NPs as a surface coating material, could be a feasible approach for controlling the pathogens. Additionally, the obtained bacterial solution data is also in agreement with the results from statistical analytical methods. PMID:25402188

  10. MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1.

    PubMed

    Dai, Yao; Zhang, Zhigao; Cao, Yongxiang; Mehta, Jawahar L; Li, Jun

    2016-03-02

    Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals.

  11. Targeting nasopharyngeal carcinoma by artesunate through inhibiting Akt/mTOR and inducing oxidative stress.

    PubMed

    Li, Qin; Ni, Wei; Deng, Zhifeng; Liu, Minghe; She, Lazhi; Xie, Qiong

    2017-01-11

    Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines. The combination of artesunate and cisplatin is synergistic in targeting NPC cells in in vitro cellular culture system and in vivo xenograft tumor models. Artesunate inhibits phosphorylation of essential molecules involved in Akt/mTOR pathway in NPC cells, such as Akt, mTOR, and 4EBP1, and its inhibitory effects are partially abolished by overexpression of constitutively active Akt. In addition, artesunate also induces mitochondrial dysfunction and oxidative stress via inhibiting mitochondrial respiration, increasing levels of mitochondrial superoxide and cellular reactive oxygen species (ROS), leading to decreased ATP levels. Two ROS scavengers partially abolish the inhibitory effects of artesunate in NPC cells. These data suggest that both inhibition of Akt/mTOR pathway and induction of ROS are required for the action of artesunate in NPC cells. Our work demonstrates that artesunate is a potential candidate for NPC treatment. Our work also highlights the critical roles of Akt/mTOR pathway and mitochondrial function in NPC cells.

  12. Low levels of graphene and graphene oxide inhibit cellular xenobiotic defense system mediated by efflux transporters.

    PubMed

    Liu, Su; Jiang, Wei; Wu, Bing; Yu, Jing; Yu, Haiyan; Zhang, Xu-Xiang; Torres-Duarte, Cristina; Cherr, Gary N

    2016-01-01

    Low levels of graphene and graphene oxide (GO) are considered to be environmentally safe. In this study, we analyzed the potential effects of graphene and GO at relatively low concentrations on cellular xenobiotic defense system mediated by efflux transporters. The results showed that graphene (<0.5 μg/mL) and GO (<20 μg/mL) did not decrease cell viability, generate reactive oxygen species, or disrupt mitochondrial function. However, graphene and GO at the nontoxic concentrations could increase calcein-AM (CAM, an indicator of membrane ATP-binding cassette (ABC) transporter) activity) accumulation, indicating inhibition of ABC transporters' efflux capabilities. This inhibition was observed even at 0.005 μg/mL graphene and 0.05 μg/mL GO, which are 100 times and 400 times lower than their lowest toxic concentration from cytotoxicity experiments, respectively. The inhibition of ABC transporters significantly increased the toxicity of paraquat and arsenic, known substrates of ABC transporters. The inhibition of ABC transporters was found to be based on graphene and GO damaging the plasma membrane structure and fluidity, thus altering functions of transmembrane ABC transporters. This study demonstrates that low levels of graphene and GO are not environmentally safe since they can significantly make cell more susceptible to other xenobiotics, and this chemosensitizing activity should be considered in the risk assessment of graphene and GO.

  13. MiR-590-5p Inhibits Oxidized- LDL Induced Angiogenesis by Targeting LOX-1

    PubMed Central

    Dai, Yao; Zhang, Zhigao; Cao, Yongxiang; Mehta, Jawahar L.; Li, Jun

    2016-01-01

    Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals- ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals. PMID:26932825

  14. Depolymerization of macrophage microfilaments prevents induction and inhibits activity of nitric oxide synthase.

    PubMed

    Fernandes, P D; Araujo, H M; Riveros-Moreno, V; Assreuy, J

    1996-12-01

    We have investigated the relationship between peritoneal murine macrophage cytoskeleton and nitric oxide (NO) synthase (NOS). Activation of the cells with lipopolysaccharide plus interferon-gamma (LI) induced iNOS, detected by nitrite or by labeled L-citrulline production and by a specific antibody against macrophage iNOS. Addition of cytochalasin B (a microfilament-depolymerizing agent) caused a dose-dependent inhibition in NO production by macrophages, whereas colchicine (a microtubule depolymerizing agent) inhibited it only by 20% and not dose-dependently. Addition of cytochalasin B together with LI abolished nitrite and L-citrulline accumulation as well as the amount of iNOS antigen in activated macrophage. Moreover, addition of cytochalasin B 6 or 12 h after stimulus, also decreased the nitrite and L-citrulline production by macrophages although iNOS antigen content by Western blot was the same in the presence or in the absence of cytochalasin B added 12 h after activation. Since cytochalasin B failed to inhibit iNOS activity directly, its inhibitory effects on NO production by macrophages is likely to be indirect, through microfilament network in central regions of cells, but not in filaments seen at pseudopodia or edging processes. Our findings demonstrate that disruption of microfilaments but not of microtubules prevents the iNOS induction process and inhibits its enzymatic activity in activated macrophages.

  15. Reactive oxygen species mediated bacterial biofilm inhibition via zinc oxide nanoparticles and their statistical determination.

    PubMed

    Dwivedi, Sourabh; Wahab, Rizwan; Khan, Farheen; Mishra, Yogendra K; Musarrat, Javed; Al-Khedhairy, Abdulaziz A

    2014-01-01

    The formation of bacterial biofilm is a major challenge in clinical applications. The main aim of this study is to describe the synthesis, characterization and biocidal potential of zinc oxide nanoparticles (NPs) against bacterial strain Pseudomonas aeruginosa. These nanoparticles were synthesized via soft chemical solution process in a very short time and their structural properties have been investigated in detail by using X-ray diffraction and transmission electron microscopy measurements. In this work, the potential of synthesized ZnO-NPs (∼ 10-15 nm) has been assessed in-vitro inhibition of bacteria and the formation of their biofilms was observed using the tissue culture plate assays. The crystal violet staining on biofilm formation and its optical density revealed the effect on biofilm inhibition. The NPs at a concentration of 100 µg/mL significantly inhibited the growth of bacteria and biofilm formation. The biofilm inhibition by ZnO-NPs was also confirmed via bio-transmission electron microscopy (Bio-TEM). The Bio-TEM analysis of ZnO-NPs treated bacteria confirmed the deformation and damage of cells. The bacterial growth in presence of NPs concluded the bactericidal ability of NPs in a concentration dependent manner. It has been speculated that the antibacterial activity of NPs as a surface coating material, could be a feasible approach for controlling the pathogens. Additionally, the obtained bacterial solution data is also in agreement with the results from statistical analytical methods.

  16. Nitric Oxide Modulates Histone Acetylation at Stress Genes by Inhibition of Histone Deacetylases1[OPEN

    PubMed Central

    Mengel, Alexander; Ageeva, Alexandra; Durner, Jörg

    2017-01-01

    Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by nitric oxide (NO); in plants, however, it is unknown whether NO affects histone acetylation. We found that treatment with the physiological NO donor S-nitrosoglutathione (GSNO) increased the abundance of several histone acetylation marks in Arabidopsis (Arabidopsis thaliana), which was strongly diminished in the presence of the NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide. This increase was likely triggered by NO-dependent inhibition of HDAC activity, since GSNO and S-nitroso-N-acetyl-dl-penicillamine significantly and reversibly reduced total HDAC activity in vitro (in nuclear extracts) and in vivo (in protoplasts). Next, genome-wide H3K9/14ac profiles in Arabidopsis seedlings were generated by chromatin immunoprecipitation sequencing, and changes induced by GSNO, GSNO/2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or trichostatin A (an HDAC inhibitor) were quantified, thereby identifying genes that display putative NO-regulated histone acetylation. Functional classification of these genes revealed that many of them are involved in the plant defense response and the abiotic stress response. Furthermore, salicylic acid, which is the major plant defense hormone against biotrophic pathogens, inhibited HDAC activity and increased histone acetylation by inducing endogenous NO production. These data suggest that NO affects histone acetylation by targeting and inhibiting HDAC complexes, resulting in the hyperacetylation of specific genes. This mechanism might operate in the plant stress response by facilitating the stress-induced transcription of genes. PMID:27980017

  17. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function

    PubMed Central

    Lê, Quang Huy; El Alaoui, Meddy; Véricel, Evelyne; Ségrestin, Bérénice; Soulère, Laurent; Guichardant, Michel; Lagarde, Michel; Moulin, Philippe; Calzada, Catherine

    2015-01-01

    Context High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). Objective The objective of our study was to investigate the effects of in vitro glycoxidized HDL, and HDL from T2D patients on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Results Compared to control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to SR-BI. Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phospholipids, namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE and 15-HETE in phospholipids (2.1, 2.1 and 2.4-fold increase respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Conclusions Altogether, our results indicate that in vitro glycoxidized HDL as well as HDL from T2D patients inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from T2D patients. PMID:25794249

  18. Inhibition and deactivation effects in catalytic wet oxidation of high-strength alcohol-distillery liquors

    SciTech Connect

    Belkacemi, K.; Larachi, F.; Hamoudi, S.; Turcotte, G.; Sayari, A.

    1999-06-01

    The removal efficiency of total organic carbon (TOC) from raw high-strength alcohol-distillery waste liquors was evaluated using three different treatments: thermolysis (T), noncatalytic wet oxidation (WO), and solid-catalyzed wet oxidation (CWO). The distillery liquors (TOC = 22,500 mg/l, sugars = 18,000 mg/l, and proteins = 13,500 mg/l) were produced by alcoholic fermentation of enzymatic hydrolyzates from steam-exploded timothy grass. TOC-abatement studies were conducted batchwise in a stirred autoclave to evaluate the influence of the catalyst (7:3, MnO{sub 2}/CeO{sub 2} mixed oxide), oxygen partial pressure (0.5--2.5 MPa), and temperature (453--523 K) on T, WO, and CWO processes. Although CWO outperformed T and WO, TOC conversions did not exceed {approximately}60% at the highest temperature used. Experiments provided prima facie evidence for a gradual fouling of the catalyst and a developing inhibition in the liquors which impaired deep TOC removals. Occurrence of catalyst deactivation by carbonaceous deposits was proven experimentally through quantitative and qualitative experiments such as elemental analysis and X-ray photoelectron spectroscopy. Inhibition toward further degradation of the liquors was ascribed to the occurrence of highly stable antioxidant intermediates via the Maillard reactions between dissolved sugars and proteins. A lumping kinetic model involving both reaction inhibition by dissolved intermediates and catalyst deactivation by carbonaceous deposits was proposed to account for the distribution of carbon in the liquid, solid, and the vapor phases.

  19. Eugenol-inhibited root growth in Avena fatua involves ROS-mediated oxidative damage.

    PubMed

    Ahuja, Nitina; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2015-02-01

    Plant essential oils and their constituent monoterpenes are widely known plant growth retardants but their mechanism of action is not well understood. We explored the mechanism of phytotoxicity of eugenol, a monoterpenoid alcohol, proposed as a natural herbicide. Eugenol (100-1000 µM) retarded the germination of Avena fatua and strongly inhibited its root growth compared to the coleoptile growth. We further investigated the underlying physiological and biochemical alterations leading to the root growth inhibition. Eugenol induced the generation of reactive oxygen species (ROS) leading to oxidative stress and membrane damage in the root tissue. ROS generation measured in terms of hydrogen peroxide, superoxide anion and hydroxyl radical content increased significantly in the range of 24 to 144, 21 to 91, 46 to 173% over the control at 100 to 1000 µM eugenol, respectively. The disruption in membrane integrity was indicated by 25 to 125% increase in malondialdehyde (lipid peroxidation byproduct), and decreased conjugated diene content (~10 to 41%). The electrolyte leakage suggesting membrane damage increased both under light as well as dark conditions measured over a period from 0 to 30 h. In defense to the oxidative damage due to eugenol, a significant upregulation in the ROS-scavenging antioxidant enzyme machinery was observed. The activities of superoxide dismutases, catalases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases were elevated by ~1.5 to 2.8, 2 to 4.3, 1.9 to 5.0, 1.4 to 3.9, 2.5 to 5.5 times, respectively, in response to 100 to 1000 µM eugenol. The study concludes that eugenol inhibits early root growth through ROS-mediated oxidative damage, despite an activation of the antioxidant enzyme machinery.

  20. UCP2 inhibition sensitizes breast cancer cells to therapeutic agents by increasing oxidative stress.

    PubMed

    Pons, Daniel Gabriel; Nadal-Serrano, Mercedes; Torrens-Mas, Margalida; Valle, Adamo; Oliver, Jordi; Roca, Pilar

    2015-09-01

    Modulation of oxidative stress in cancer cells plays an important role in the study of the resistance to anticancer therapies. Uncoupling protein 2 (UCP2) may play a dual role in cancer, acting as a protective mechanism in normal cells, while its overexpression in cancer cells could confer resistance to chemotherapy and a higher survival through downregulation of ROS production. Thus, our aim was to check whether the inhibition of UCP2 expression and function increases oxidative stress and could render breast cancer cells more sensitive to cisplatin (CDDP) or tamoxifen (TAM). For this purpose, we studied clonogenicity, mitochondrial membrane potential (ΔΨm), cell viability, ROS production, apoptosis, and autophagy in MCF-7 and T47D (only the last four determinations) breast cancer cells treated with CDDP or TAM, in combination or without a UCP2 knockdown (siRNA or genipin). Furthermore, survival curves were performed in order to check the impact of UCP2 expression in breast cancer patients. UCP2 inhibition and cytotoxic treatments produced a decrease in cell viability and clonogenicity, in addition to an increase in ΔΨm, ROS production, apoptosis, and autophagy. It is important to note that CDDP decreased UCP2 protein levels, so that the greatest effects produced by the UCP2 inhibition in combination with a cytotoxic treatment, with regard to treatment alone, were observed in TAM+UCP2siRNA-treated cells. Moreover, this UCP2 inhibition caused autophagic cell death, since apoptosis parameters barely increased after UCP2 knockdown. Finally, survival curves revealed that higher UCP2 expression corresponded with a poorer prognosis. In conclusion, UCP2 could be a therapeutic target in breast cancer, especially in those patients treated with tamoxifen.

  1. PARP-1 inhibition influences the oxidative stress response of the human lens

    PubMed Central

    Smith, Andrew J.O.; Ball, Simon S.R.; Bowater, Richard P.; Wormstone, I. Michael

    2016-01-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is best characterised for its involvement in DNA repair. PARP-1 activity is also linked to cell fate, confounding its roles in maintaining genome integrity. The current study assessed the functional roles of PARP-1 within human lens cells in response to oxidative stress. The human lens epithelial cell line FHL124 and whole human lens cultures were used as experimental systems. Hydrogen peroxide (H2O2) was employed to induce oxidative stress and cell death was assessed by LDH release. The functional influence of PARP-1 was assessed using targeted siRNA and chemical inhibition (by AG14361). Immunocytochemistry and western blotting were used to assess PARP-1 expression and the alkaline comet assay determined the levels of DNA strand breaks. PARP-1 was generally observed in the cell nucleus in both the FHL124 cell line and whole human lenses. PARP-1 inhibition rendered FHL124 cells more susceptible to H2O2-induced DNA strand breaks. Interestingly, reduction of PARP-1 activity significantly inhibited H2O2-induced cell death relative to control cells. Inhibition of PARP-1 in whole human lenses resulted in a reduced level of lens opacity and cell death following exposure to H2O2 relative to matched pair controls. Thus, we show that PARP-1 could play a role in the fate of human lens cells, and these first observations in human lenses suggest that it could impact on lens opacity. Further studies are required to elucidate the regulatory processes that give rise to these effects. PMID:26990173

  2. Inhibition of NF-kappaB DNA binding by nitric oxide.

    PubMed Central

    Matthews, J R; Botting, C H; Panico, M; Morris, H R; Hay, R T

    1996-01-01

    It has been suggested that the NF-kappaB transcription factor family may mediate expression of the gene encoding the cytokine-inducible form of nitric oxide synthase (iNOS). To establish if nitric oxide (NO) could in turn affect activity of NF-kappaB, the ability of NO-donor compounds to influence NF-kappaB DNA binding activity in vitro was investigated. NO-donor compounds sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) both inhibited the DNA binding activity of recombinant NF-kappaB p50 and p65 homodimers and of p50-p65 heterodimers. Inhibition of NF-kappaB p50 DNA binding by NO-donor compounds involved modification of the conserved redox-sensitive C62 residue, as a C62S p50 mutant was significantly more resistant to SNP-mediated inactivation. Non-reducing SDS-polyacrylamide gel electrophoresis demonstrated that SNP could inhibit p50 DNA binding by mechanisms other than the formation of intersubunit disulphide bonds involving p50 residue C62. Electrospray ionization mass spectrometry of a synthetic NF-kappaB p5O peptide containing the C62 residue suggested that NO gas can modify C62 by S-nitrosylation. This study indicates that NO-donors can directly inhibit the DNA binding activity of NF-kappaB family proteins, suggesting that cellular NO provides another control mechanism for modulating the expression of NF-kappaB-responsive genes. PMID:8710491

  3. Synthesis, nitric oxide release, and α-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives.

    PubMed

    Wang, Qi-Qin; Cheng, Ning; Yi, Wen-Bing; Peng, Sheng-Ming; Zou, Xiao-Qing

    2014-03-01

    α-Glucosidase (AG) play crucial roles in the digestion of carbohydrates. Inhibitors of α-glucosidase (AGIs) are promising candidates for the development of anti-diabetic drugs. Here, five series of apigenin and chrysin nitric oxide (NO)-donating derivatives were synthesised and evaluated for their AG inhibitory activity and NO releasing capacity in vitro. Except for 9a-c, twelve compounds showed remarkable inhibitory activity against α-glucosidase, with potency being better than that of acarbose and 1-deoxynojirimycin. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure activity relationship studies indicated that 5-OH, hydrophobic coupling chain, and carbonyl groups of the coupling chain could enhance the inhibitory activity. Apigenin and chrysin derivatives therefore represents a new class of promising compounds that can inhibit α-glucosidase activity and supply moderate NO for preventing the development of diabetic complications.

  4. Daily sesame oil supplement attenuates joint pain by inhibiting muscular oxidative stress in osteoarthritis rat model.

    PubMed

    Hsu, Dur-Zong; Chu, Pei-Yi; Jou, I-Ming

    2016-03-01

    Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the population. The aim of this study was to evaluate the efficacy of sesame oil in controlling OA pain in rats. Rat joint pain was induced by medial meniscal transection in Sprague-Dawley rats and assessed by using hindlimb weight distribution method. Muscular oxidative stress was assessed by determining lipid peroxidation, reactive oxygen species and circulating antioxidants. Sesame oil significantly decreased joint pain compared with positive control group in a dose-dependent manner. Sesame oil decreased lipid peroxidation in muscle but not in serum. Further, sesame oil significantly decreased muscular superoxide anion and peroxynitrite generations but increased muscular glutathione and glutathione peroxidase levels. Further, sesame oil significantly increased nuclear factor erythroid-2-related factor (Nrf2) expression compared with positive control group. We concluded that daily sesame oil supplement may attenuate early joint pain by inhibiting Nrf2-associated muscular oxidative stress in OA rat model.

  5. Inhibition of retinol oxidation by ethanol in the rat liver and colon

    PubMed Central

    Parlesak, A; Menzl, I; Feuchter, A; Bode, J; Bode, C

    2000-01-01

    BACKGROUND—Epidemiological evidence has been presented for an increased risk of development of colon cancer after chronic alcohol abuse. Alcohol is degraded by cytosolic alcohol dehydrogenases that also are capable of retinol oxidation. Inhibition of retinol oxidation to retinoic acid has been shown to occur in parallel with profound impairment of intracellular retinoid signal transduction and loss of cell differentiation control.
AIMS—In the present study, the change in cytosolic retinol oxidation and retinoic acid formation by ethanol concentrations that occur in body tissues in humans after social drinking was measured in cells from the liver, and small and large intestine of the rat.
RESULTS—The specific catalytic efficiency Vmax/Km (ml/min/g) of cytosolic retinol oxidation in the large intestine (28.9) was found to be distinctly higher than that in the liver (3.4), while the efficiency in the small intestine was negligible (0.20). In the presence of increasing ethanol concentrations (9, 17, and 34 mM), Vmax/Km for retinol oxidation decreased in a dose dependent manner to 7.8% of the initial value in the large intestine and to 12% in the liver. The Vmax/Km of retinoic acid formation in the liver cytosol decreased to 15%.
CONCLUSIONS—Our data demonstrate impairment of hepatic and intestinal cytosolic retinol oxidation and retinoic acid formation by ethanol at concentrations in body tissues after social drinking in humans. The results suggest that the increased risk of developing colorectal neoplasias after alcohol abuse may, at least in part, be caused by impaired retinoid signal transduction.


Keywords: retinol; retinoic acid; ethanol; alcohol; alcohol dehydrogenases; intestine PMID:11076882

  6. Tyrosol attenuates ischemia-reperfusion-induced kidney injury via inhibition of inducible nitric oxide synthase.

    PubMed

    Wang, Pengqi; Zhu, Qingjun; Wu, Nan; Siow, Yaw L; Aukema, Harold; O, Karmin

    2013-04-17

    Tyrosol is a natural phenolic antioxidant compound. Oxidative stress represents one of the important mechanisms underlying ischemia-reperfusion-induced kidney injury. The aim of this study was to investigate the effect of tyrosol against ischemia-reperfusion-induced acute kidney injury. The left kidney of Sprague-Dawley rats was subjected to 45 min of ischemia followed by reperfusion for 6 h. Ischemia-reperfusion caused an increase in peroxynitrite formation and lipid peroxidation. The level of nitric oxide (NO) metabolites and the mRNA of inducible nitric oxide synthase (iNOS) were elevated in ischemia-reperfused kidneys. Administration of tyrosol (100 mg/kg body weight) to rats prior to the induction of ischemia significantly reduced peroxynitrite formation, lipid peroxidation, and the level of NO metabolites. Tyrosol administration also attenuated ischemia-reperfusion-induced NF-κB activation and iNOS expression. Such a treatment improved kidney function. Results suggest that tyrosol may have a protective effect against acute kidney injury through inhibition of iNOS-mediated oxidative stress.

  7. N-acetylcysteine inhibits in vivo oxidation of native low-density lipoprotein

    PubMed Central

    Cui, Yuqi; Narasimhulu, Chandrakala A.; Liu, Lingjuan; Zhang, Qingbin; Liu, Patrick Z.; Li, Xin; Xiao, Yuan; Zhang, Jia; Hao, Hong; Xie, Xiaoyun; He, Guanglong; Cui, Lianqun; Parthasarathy, Sampath; Liu, Zhenguo

    2015-01-01

    Low-density lipoprotein (LDL) is non-atherogenic, while oxidized LDL (ox-LDL) is critical to atherosclerosis. N-acetylcysteine (NAC) has anti-atherosclerotic effect with largely unknown mechanisms. The present study aimed to determine if NAC could attenuate in vivo LDL oxidation and inhibit atherosclerosis. A single dose of human native LDL was injected intravenously into male C57BL/6 mice with and without NAC treatment. Serum human ox-LDL was detected 30 min after injection, reached the peak in 3 hours, and became undetectable in 12 hours. NAC treatment significantly reduced serum ox-LDL level without detectable serum ox-LDL 6 hours after LDL injection. No difference in ox-LDL clearance was observed in NAC-treated animals. NAC treatment also significantly decreased serum ox-LDL level in patients with coronary artery diseases and hyperlipidemia without effect on LDL level. Intracellular and extracellular reactive oxidative species (ROS) production was significantly increased in the animals treated with native LDL, or ox-LDL and in hyperlipidemic LDL receptor knockout (LDLR−/−) mice that was effectively prevented with NAC treatment. NAC also significantly reduced atherosclerotic plaque formation in hyperlipidemic LDLR−/− mice. NAC attenuated in vivo oxidation of native LDL and ROS formation from ox-LDL associated with decreased atherosclerotic plaque formation in hyperlipidemia. PMID:26536834

  8. Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients with inflammatory bowel disease.

    PubMed

    Najafzadeh, Mojgan; Reynolds, P Dominic; Baumgartner, Adolf; Jerwood, David; Anderson, Diana

    2007-01-01

    Inflammatory Bowel Disease (IBD) is partly caused by oxidative stress from free radicals and reduced antioxidant levels. Using hydrogen peroxide to induce oxidative stress in vitro in peripheral lymphocytes we investigated the induction of DNA damage supplemented with ethanolic extract of Chaga mushroom as a protective antioxidant. Lymphocytes were obtained from 20 IBD patients and 20 healthy volunteers. For treatment, a constant H_{2}O_{2 } dose (50 microg/ml) was used with variable doses of Chaga extract (10-500 microg/ml). DNA damage was evaluated in 50 cells per individual and dose using the Comet assay (making 1000 observations per experimental point ensuring appropriate statistical power). Chaga supplementation resulted in a 54.9% (p < 0.001) reduction of H_{2}O_{2 } induced DNA damage within the patient group and 34.9% (p < 0.001) within the control group. Lymphocytes from Crohn's disease (CD) patients had a greater basic DNA damage than Ulcerative Colitis (UC) patients (p < 0.001). Conclusively, Chaga extract reduces oxidative stress in lymphocytes from IBD patients and also healthy individuals when challenged in vitro. Thus, Chaga extract could be a possible and valuable supplement to inhibit oxidative stress in general.

  9. Intermedin ameliorates IgA nephropathy by inhibition of oxidative stress and inflammation.

    PubMed

    Wang, Yanhong; Tian, Jihua; Guo, Haixiu; Mi, Yang; Zhang, Ruijing; Li, Rongshan

    2016-05-01

    IgA nephropathy (IgAN) is the most frequent form of glomerulonephritis worldwide. The role of oxidative stress and inflammation in the pathogenesis of IgAN has been reported. Intermedin (IMD) is a newly discovered peptide that is closely related to adrenomedullin. We have recently reported that IMD can significantly reduce renal ischemia/reperfusion injury by diminishing oxidative stress and suppressing inflammation. The present study was designed to explore whether IMD ameliorates IgAN via oxidative stress- and inflammation-dependent mechanisms. Our results showed that IMD administration resulted in the prevention of albuminuria and ameliorated renal pathomorphological changes. These findings were associated with (1) decreased renal TGF-β1 and collagen IV expression, (2) an increased SOD level and reduced MDA level, (3) the inhibition of the renal activation of NF-κB p65 and (4) the downregulation of the expression of inflammatory factors (TNF-α, MCP-1 and MMP-9) in the kidney. These results indicate that IMD in the kidney protects against IgAN by reducing oxidative stress and suppressing inflammation.

  10. Nitric oxide regulates nitric oxide synthase-2 gene expression by inhibiting NF-kappaB binding to DNA.

    PubMed Central

    Park, S K; Lin, H L; Murphy, S

    1997-01-01

    Treatment of astroglial cells with interleukin 1beta and interferon gamma transcriptionally activates the nitric oxide synthase (NOS)-2 gene. The duration of mRNA expression is brief because of transcript instability. In addition, NO donors reduce the expression of NOS-2 mRNA dramatically by reducing the rate of transcription. In this study we observed that the NO donor, spermine NONOate did not inhibit the activation and translocation of NF-kappaB, a key transcription factor in the induction of NOS-2, but inhibited formation of the NF-kappaB-DNA complex. This effect was reversed by methaemoglobin (acting as an NO trap) and by the reducing agent dithiothreitol. Formation of the interferon-regulatory factor-DNA complex was unaffected by NO. These results suggest that NO can modulate its own production by interfering with NF-kappaB interaction with the promoter region of the NOS gene, a negative feedback effect that may be important for limiting NO production in vivo. PMID:9065784

  11. Arginase inhibition in airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin

    SciTech Connect

    Bratt, Jennifer M.; Franzi, Lisa M.; Linderholm, Angela L.; O'Roark, Erin M.; Kenyon, Nicholas J.; Last, Jerold A.

    2010-01-01

    Arginase1 and nitric oxide synthase2 (NOS2) utilize L-arginine as a substrate, with both enzymes expressed at high levels in the asthmatic lung. Inhibition of arginase in ovalbumin-exposed C57BL/6 mice with the transition state inhibitor N{sup o}mega-hydroxy-nor-L-arginine (nor-NOHA) significantly increased total L-arginine content in the airway compartment. We hypothesized that such an increase in L-arginine content would increase the amount of nitric oxide (NO) being produced in the airways and thereby decrease airway hyperreactivity and eosinophilic influx. We further hypothesized that despite arginase inhibition, NOS2 knockout (NOS2-/-) mice would be unable to up-regulate NO production in response to allergen exposure and would demonstrate higher amounts of airway hyperreactivity and eosinophilia under conditions of arginase inhibition than C57BL/6 animals. We found that administration of nor-NOHA significantly decreased airway hyperreactivity and eosinophilic airway inflammation in ovalbumin-exposed C57BL/6 mice, but these parameters were unchanged in ovalbumin-exposed NOS2-/- mice. Arginase1 protein content was increased in mice exposed to ovalbumin, an effect that was reversed upon nor-NOHA treatment in C57BL/6 mice. Arginase1 protein content in the airway compartment directly correlated with the degree of airway hyperreactivity in all treatment groups. NOS2-/- mice had significantly greater arginase1 and arginase2 concentrations compared to their respective C57BL/6 groups, indicating that inhibition of arginase may be dependent upon NOS2 expression. Arginase1 and 2 content were not affected by nor-NOHA administration in the NOS2-/- mice. We conclude that L-arginine metabolism plays an important role in the development of airway hyperreactivity and eosinophilic airway inflammation. Inhibition of arginase early in the allergic inflammatory response decreases the severity of the chronic inflammatory phenotype. These effects appear to be attributable to NOS2

  12. Inhibition of bacterial adhesion and biofilm formation by dual functional textured and nitric oxide releasing surfaces.

    PubMed

    Xu, Li-Chong; Wo, Yaqi; Meyerhoff, Mark E; Siedlecki, Christopher A

    2017-03-15

    In separate prior studies, physical topographic surface modification or nitric oxide (NO) release has been demonstrated to each be an effective approach to inhibit and control bacterial adhesion and biofilm formation on polymeric surfaces. Such approaches can prevent biomaterial-associated infection without causing the antibiotic resistance of the strain. In this work, both techniques were successfully integrated and applied to a polyurethane (PU) biomaterial surface that bears ordered pillar topographies (400/400nm and 500/500nm patterns) at the top surface and a S-nitroso-N-acetylpenicillamine (SNAP, NO donor) doped sub-layer in the middle, via a soft lithography two-stage replication process. Upon placing the SNAP textured PU films into PBS at 37°C, the decomposition of SNAP within polymer film initiates NO release with a lifetime of up to 10days at flux levels >0.5×10(-10)molmin(-1)cm(-2) for a textured polyurethane layer containing 15wt% SNAP. The textured surface reduces the accessible surface area and the opportunity of bacteria-surface interaction, while the NO release from the same surface further inhibits bacterial growth and biofilm formation. Such dual functionality surfaces are shown to provide a synergistic effect on inhibition of Staphylococcus epidermidis bacterial adhesion that is significantly greater than the inhibition of bacterial adhesion achieved by either single treatment approach alone. Longer term experiments to observe biofilm formation demonstrate that the SNAP doped-textured PU surface can inhibit the biofilm formation for >28d and provide a practical approach to improve the biocompatibility of current biomimetic biomaterials and thereby reduce the risk of pathogenic infection.

  13. Tat-HSP22 inhibits oxidative stress-induced hippocampal neuronal cell death by regulation of the mitochondrial pathway.

    PubMed

    Jo, Hyo Sang; Kim, Dae Won; Shin, Min Jea; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Yeo, Hyeon Ji; Sohn, Eun Jeong; Son, Ora; Cho, Sung-Woo; Kim, Duk-Soo; Yu, Yeon Hee; Lee, Keun Wook; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2017-01-04

    Oxidative stress plays an important role in the progression of various neuronal diseases including ischemia. Heat shock protein 22 (HSP22) is known to protect cells against oxidative stress. However, the protective effects and mechanisms of HSP22 in hippocampal neuronal cells under oxidative stress remain unknown. In this study, we determined whether HSP22 protects against hydrogen peroxide (H2O2)-induced oxidative stress in HT-22 using Tat-HSP22 fusion protein. We found that Tat-HSP22 transduced into HT-22 cells and that H2O2-induced cell death, oxidative stress, and DNA damage were significantly reduced by Tat-HSP22. In addition, Tat-HSP22 markedly inhibited H2O2-induced mitochondrial membrane potential, cytochrome c release, cleaved caspase-3, and Bax expression levels, while Bcl-2 expression levels were increased in HT-22 cells. Further, we showed that Tat-HSP22 transduced into animal brain and inhibited cleaved-caspase-3 expression levels as well as significantly inhibited hippocampal neuronal cell death in the CA1 region of animals in the ischemic animal model. In the present study, we demonstrated that transduced Tat-HSP22 attenuates oxidative stress-induced hippocampal neuronal cell death through the mitochondrial signaling pathway and plays a crucial role in inhibiting neuronal cell death, suggesting that Tat-HSP22 protein may be used to prevent oxidative stress-related brain diseases including ischemia.

  14. Lycopene inhibits LPS-induced proinflammatory mediator inducible nitric oxide synthase in mouse macrophage cells.

    PubMed

    Rafi, Mohamed M; Yadav, Prem Narayan; Reyes, Marynell

    2007-01-01

    Lycopene is a fat-soluble red-orange carotenoid found primarily in tomatoes and tomato-derived products, including tomato sauce, tomato paste, and ketchup, and other dietary sources, including dried apricots, guava, watermelon, papaya, and pink grapefruit. In this study, we have demonstrated the molecular mechanism underlying the anti-inflammatory properties of lycopene using a mouse macrophage cell line (RAW 264.7). Treatment with lycopene (10 microM) inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production (40% compared with the control). Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that lycopene treatment decreased LPS-induced inducible nitric oxide synthase (iNOS) protein and mRNA expression in RAW 264.7 cells, respectively. These results suggest that lycopene has anti-inflammatory activity by inhibiting iNOS proteins and mRNA expressions in mouse macrophage cell lines. Furthermore, cyclooxygenase-2 (COX-2) protein and mRNA expression were not affected by treatment with lycopene.

  15. Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy.

    PubMed

    Vaya, Jacob; Mahmood, Saeed; Goldblum, Amiram; Aviram, Michael; Volkova, Nina; Shaalan, Amin; Musa, Ramadan; Tamir, Snait

    2003-01-01

    Twenty flavonoid compounds of five different subclasses were selected, and the relationship of their structure to the inhibition of low-density lipoprotein (LDL) oxidation in vitro was investigated. The most effective inhibitors, by either copper ion or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) induction, were flavonols and/or flavonoids with two adjacent hydroxyl groups at ring B. In the presence of the later catechol group, the contribution of the double bond and the carbonyl group at ring C was negligible. Isoflavonoids were more effective inhibitors than other flavonoid subclasses with similar structure. Substituting ring B with hydroxyl group(s) at 2' position resulted in a significantly higher inhibitory effect than by substituting ring A or ring B at other positions. The type of LDL inducer had no effect in flavonoids with catechol structure. Calculated heat of formation data (deltadeltaH(f)) revealed that the donation of a hydrogen atom from position 3 was the most likely result, followed by that of a hydroxyl from ring B. Position 3 was favored only in the presence of conjugated double bonds between ring A to ring B. This study makes it possible to assign the contribution of different functional groups among the flavonoid subclasses to in vitro inhibition of LDL oxidation.

  16. Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway.

    PubMed

    Wen, Di; An, Meiling; Gou, Hongyan; Liu, Xia; Liu, Li; Ma, Chunling; Cong, Bin

    2016-12-01

    As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (METH) abuse may lead to long-lasting abnormalities in brain structure and function. We found that pretreatment of cholecystokinin-8 (CCK-8) inhibited METH-induced brain cellular dopaminergic (DA) damage in the striatum and substantia nigra, and related behavioural deficits and hyperthermia. However, the mechanism of CCK-8 action on METH-induced toxicity is not clear. The aim of this study was to explore whether the possible protective effect of CCK-8 on METH-induced neurotoxicity involved anti-oxidative stress mechanisms. The subtypes of CCK receptors mediating the regulatory action of CCK-8 were also investigated. The present results revealed that CCK-8 dose-dependently inhibited METH-induced cytotoxic effect by activating the CCK2 receptor subtype in PC12 cells and CCK2 receptor stable transfected-HEK293 cells. Pre-treatment of CCK-8 before METH stimulation significantly attenuated the generation of reactive oxygen species and NADPH oxidase activation in PC12 cells. In conclusion, our study demonstrated a protective effect of CCK-8 on METH-induced neurotoxicity in vitro and suggested that a possible mechanism of this action was dependent on the activation of the CCK2 receptor to reduce the neurotoxicity and oxidative stress induced by METH stimulation.

  17. Copper-dependent inhibition and oxidative inactivation with affinity cleavage of yeast glutathione reductase.

    PubMed

    Murakami, Keiko; Tsubouchi, Ryoko; Fukayama, Minoru; Yoshino, Masataka

    2014-06-01

    Effects of copper on the activity and oxidative inactivation of yeast glutathione reductase were analyzed. Glutathione reductase from yeast was inhibited by cupric ion and more potently by cuprous ion. Copper ion inhibited the enzyme noncompetitively with respect to the substrate GSSG and NADPH. The Ki values of the enzyme for Cu(2+) and Cu(+) ion were determined to be 1 and 0.35 μM, respectively. Copper-dependent inactivation of glutathione reductase was also analyzed. Hydrogen peroxide and copper/ascorbate also caused an inactivation with the cleavage of peptide bond of the enzyme. The inactivation/fragmentation of the enzyme was prevented by addition of catalase, suggesting that hydroxyl radical produced through the cuprous ion-dependent reduction of oxygen is responsible for the inactivation/fragmentation of the enzyme. SDS-PAGE and TOF-MS analysis confirmed eight fragments, which were further determined to result from the cleavage of the Met17-Ser18, Asn20-Thr21, Glu251-Gly252, Ser420-Pro421, Pro421-Thr422 bonds of the enzyme by amino-terminal sequencing analysis. Based on the kinetic analysis and no protective effect of the substrates, GSSG and NADPH on the copper-mediated inactivation/fragmentation of the enzyme, copper binds to the sites apart from the substrate-sites, causing the peptide cleavage by hydroxyl radical. Copper-dependent oxidative inactivation/fragmentation of glutathione reductase can explain the prooxidant properties of copper under the in vivo conditions.

  18. Gene Therapy Inhibiting Neointimal Vascular Lesion: In vivo Transfer of Endothelial Cell Nitric Oxide Synthase Gene

    NASA Astrophysics Data System (ADS)

    von der Leyen, Heiko E.; Gibbons, Gary H.; Morishita, Ryuichi; Lewis, Neil P.; Zhang, Lunan; Nakajima, Masatoshi; Kaneda, Yasufumi; Cooke, John P.; Dzau, Victor J.

    1995-02-01

    It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as β-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessel. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia.

  19. Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase.

    PubMed Central

    Kasten, T P; Collin-Osdoby, P; Patel, N; Osdoby, P; Krukowski, M; Misko, T P; Settle, S L; Currie, M G; Nickols, G A

    1994-01-01

    We have examined the effects of modulating nitric oxide (NO) levels on osteoclast-mediated bone resorption in vitro and the effects of nitric oxide synthase (NOS) inhibitors on bone mineral density in vivo. Diaphorase-based histochemical staining for NOS activity of bone sections or highly enriched osteoclast cultures suggested that osteoclasts exhibit substantial NOS activity that may account for basal NO production. Chicken osteoclasts were cultured for 36 hr on bovine bone slices in the presence or absence of the NO-generating agent sodium nitroprusside or the NOS inhibitors N-nitro-L-arginine methyl ester and aminoguanidine. Nitroprusside markedly decreased the number of bone pits and the average pit area in comparison with control cultures. On the other hand, NOS inhibition by N-nitro-L-arginine methyl ester or aminoguanidine dramatically increased the number of bone pits and the average resorption area per pit. In a model of osteoporosis, aminoguanidine potentiated the loss of bone mineral density in ovariectomized rats. Aminoguanidine also caused a loss of bone mineral density in the sham-operated rats. Inhibition of NOS activity in vitro and in vivo resulted in an apparent potentiation of osteoclast activity. These findings suggest that endogenous NO production in osteoclast cultures may regulate resorption activity. The modulation of NOS and NO levels by cells within the bone microenvironment may be a sensitive mechanism for local control of osteoclast bone resorption. Images PMID:7513424

  20. Circuit analysis and simulation of an ultrahigh-frequency capacitance sensor for scanning capacitance microscopy

    NASA Astrophysics Data System (ADS)

    Yang, Jing; Postula, A.; Bialkowski, M.

    2004-03-01

    Quantitative two-dimensional dopant profiling tools are urgently needed for nowadays semiconductor industry. Scanning Capacitance Microscopy (SCM) holds most promise to become such a tool. The key component of SCM is an ultra high frequency (UHF) capacitance sensor. The output of the sensor has been approximately regarded as dC/dV, the derivative of the capacitance between the SCM tip and the sample versus the applied bias voltage. The SCM dopant profiling involves extracting the dopant profile from the SCM signal using analytic or numerical simulation models of Metal-Oxide-Semiconductor physics. To achieve a quantitative SCM dopant profiling, the operational principle of the whole SCM measurement has to be well understood and correctly included in those models. Recently, experimental evidences show the SCM signal is dramatically affected by many SCM experimental factors, including the behavior of the UHF capacitance sensor. However, till now, very little research has been reported on the behavior of the sensor in SCM measurement of semiconductors. In this paper, we derive an analytic expression of the sensor output, a circuit simulation model of the sensor is established using Advanced Design System 2003, and the dependences of the sensor output on the SCM operational factors are simulated.

  1. Nitric oxide synthase inhibition attenuates cutaneous vasodilation during the post-menopausal hot flash

    PubMed Central

    Hubing, Kimberly A.; Wingo, Jonathan E.; Brothers, R. Matthew; Coso, Juan Del; Low, David A.; Crandall, Craig G.

    2010-01-01

    Objective The purpose of this study was to test the hypothesis that local inhibition of nitric oxide and prostaglandin synthesis attenuates cutaneous vasodilator responses during post-menopausal hot flashes. Methods Four microdialysis membranes were inserted into forearm skin (dorsal surface) of 8 post-menopausal women (mean ± SD, 51±7 y). Ringers solution (control), 10mM Ketorolac (Keto) to inhibit prostaglandin synthesis, 10mM NG-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase, and a combination of 10mM Keto + 10mM L-NAME were each infused at the separate sites. Skin blood flow at each site was indexed using laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial blood pressure and was expressed as a percentage of the maximal calculated CVC (CVCmax) obtained following infusion of 50mM sodium nitropruside at all sites at the end of the study. Data from 13 hot flashes were analyzed. Results At the control site, the mean ± SD peak increase in CVC was 15.5±6% CVCmax units. This value was not different relative to the peak increase in CVC at the Keto site (13.0±5 % CVCmax units, P = 0.09). However, the peak increase in CVC during the flash was attenuated at the L-NAME and L-NAME + Keto sites (7.4±4 % CVCmax units and 8.7±7 % CVCmax units, respectively) relative to both the control and the Keto sites (P<0.05 for both comparisons). There were no significant differences in the peak increases in sweat rate between any of the sites (P = 0.24). Conclusions These data demonstrate that cutaneous vasodilation during a hot flash has a nitric oxide component. Increases in CVC despite the inhibition of prostaglandin synthesis suggest prostaglandins do not contribute to cutaneous vasodilation during a hot flash. PMID:20505548

  2. Inhibition of LDL oxidation by a new estradiol receptor modulator compound LY-139478, comparative effect with other steroids.

    PubMed

    Rattan, A K; Arad, Y

    1998-02-01

    Oxidation of low-density lipoprotein (LDL) is postulated to be essential for the development of atherosclerosis. LY-139478 is a new non-steroidal potent estrogen analog, but its effects on in vitro LDL oxidation have not been completely elucidated. We investigated the ability of LY-139478 to inhibit in vitro copper sulfate-mediated LDL oxidation using several methods, including conjugated diene (CD) accumulation, relative electrophoretic mobility on agarose gel, thiobarbituric acid-reactive substances (TBARS) assay, and superoxide anions scavenging activity. The antioxidative potential of LY-139478 was compared to testosterone (T), 17-alpha-estradiol (17alphaE), 17-beta-estradiol (17betaE), dehydroepiandrosterone (D), and dehydroepiandrosterone-3-sulfate (DS). LY-139478 was superior to 17alphaE and 17betaE in prolonging the lag phase and decreasing the slope and peak concentration of the conjugated diene accumulation, decreasing the rate of migration of LDL on agarose gel electrophoresis, and inhibiting the production of melonyldialdehyde (MDA) in the TBARS assay. T, D and DS were ineffective in all three assays. It was previously shown that when native LDL is oxidized by previously oxidized LDL (secondary oxidation) the lag phase is lost (Schnitzer et al. Free Rad Res 1995;23:137). LY-139478 was at least 15-fold more effective than 17alphaE, and 17betaE in slowing the propagation phase and reducing CD accumulation in this secondary oxidation, with 50% inhibition at 10 microM and 98% inhibition at 100 microM. However, none restored the lag phase. T, D and DS were ineffective. Superoxide anion generation was inhibited only by DS at high doses (500 microM). These results demonstrate that LY-139478 is an effective inhibitor of LDL oxidation and is superior to natural steroidal hormones, including 17betaE, in protecting against primary and secondary LDL oxidation.

  3. The Inhibition of Pb(IV) Oxide Formation in Chlorinated Water by Orthophosphate

    SciTech Connect

    Lytle, Darren A.; Schock, Michael R.; Scheckel, Kirk; EPA

    2009-10-05

    Historically, understanding lead solubility and its control in drinking water has been based on Pb(II) chemistry. Unfortunately, there is very little information available regarding the nature of Pb(IV) oxides in finished drinking water and water distribution systems, and the conditions under which they persist. The objective of this research was to explore the impact of orthophosphate on the realistic pathways that lead to the formation of Pb(IV) oxides in chlorinated water. The results of XRD and XANES analysis showed that, in the absence of orthophosphate (DIC = 10 mg C/L, 24 C, pH 7.75-8.1, 3 mg Cl{sub 2}/L goal), Pb(IV) oxides formed with time following a transformation from the Pb(II) mineral hydrocerussite. Under the same experimental conditions, orthophosphate dosing inhibited the formation of Pb(IV) oxides. The Pb(II) mineral hydroxypyromorphite, Pb{sub 5}(PO{sub 4}){sub 3}OH, was the only mineral phase identified during the entire study of over 600 days, although the presence of some chloropyromorphite, Pb{sub 5}(PO{sub 4}){sub 3}Cl, could not be ruled out. The conclusions were further supported by SEM, TEM, and XANES analysis of lead colloids, and lead precipitation experiments conducted in the absence of free chlorine. The findings provide an important explanation for the absence of Pb(IV) oxides in some water systems that have used, or currently use, orthophosphate for corrosion control when otherwise, based on disinfection practices and water quality, its presence would be anticipated, as well as why the conversion from free chlorine to chloramines was not observed to increase lead release.

  4. The inhibition of Pb(IV) oxide formation in chlorinated water by orthophosphate.

    PubMed

    Lytle, Darren A; Schock, Michael R; Scheckel, Kirk

    2009-09-01

    Historically, understanding lead solubility and its control in drinking water has been based on Pb(II) chemistry. Unfortunately, there is very little information available regarding the nature of Pb(IV) oxides in finished drinking water and water distribution systems, and the conditions under which they persist. The objective of this research was to explore the impact of orthophosphate on the realistic pathways that lead to the formation of Pb(IV) oxides in chlorinated water. The results of XRD and XANES analysis showed that, in the absence of orthophosphate (DIC = 10 mg C/L, 24 degrees C, pH 7.75-8.1, 3 mg Cl2/L goal), Pb(IV) oxides formed with time following a transformation from the Pb(II) mineral hydrocerussite. Under the same experimental conditions, orthophosphate dosing inhibited the formation of Pb(IV) oxides. The Pb(II) mineral hydroxypyromorphite, Pb5(PO4)3OH, was the only mineral phase identified during the entire study of over 600 days, although the presence of some chloropyromorphite, Pb5(PO4)3Cl, could not be ruled out The conclusions were further supported by SEM, TEM, and XANES analysis of lead colloids, and lead precipitation experiments conducted in the absence of free chlorine. The findings provide an important explanation for the absence of Pb(IV) oxides in some water systems that have used, or currently use, orthophosphate for corrosion control when otherwise, based on disinfection practices and water quality, its presence would be anticipated, as well as why the conversion from free chlorine to chloramines was not observed to increase lead release.

  5. Inhibition of inducible Nitric Oxide Synthase by a mustard gas analog in murine macrophages

    PubMed Central

    Qui, Min; Paromov, Victor M; Yang, Hongsong; Smith, Milton; Stone, William L

    2006-01-01

    Background 2-Chloroethyl ethyl sulphide (CEES) is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2'-dichlorodiethyl sulphide, or sulphur mustard gas (HD). Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS) enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO) production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS) activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing. Results We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours) in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA) or dichlorofluorescin diacetate (DCFH-DA). Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEES in vitro did not inhibit its enzymatic activity Conclusion CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-κB) signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS-stimulated macrophages could elevate

  6. 5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats.

    PubMed

    García-Pedraza, José-Ángel; García, Mónica; Martín, María-Luisa; Morán, Asunción

    2015-09-01

    Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3±1.0, 43.7±2.7 and 66.7±4.0 for 2, 4 and 6Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT1/7 agonist) (0.00000125-0.1μg/kg each) or l-694,247 (5-HT1D agonist; 0.0125μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT2), 1-PBG (5-HT3), cisapride (5-HT4), AS-19 (5-HT7), CGS-12066B (5-HT1B) or 8-OH-DPAT (5-HT1A) (0.0125μg/kg each). The effect of l-694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT1D; 1mg/kg) or l-NAME (nitric oxide; 10mg/kg), but not by indomethacin (COX1/2; 2mg/kg) or glibenclamide (ATP-dependent K(+) channel; 20mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT1D receptors via nitric oxide release.

  7. Mobile phone radiation inhibits Vigna radiata (mung bean) root growth by inducing oxidative stress.

    PubMed

    Sharma, Ved Parkash; Singh, Harminder Pal; Kohli, Ravinder Kumar; Batish, Daizy Rani

    2009-10-15

    During the last couple of decades, there has been a tremendous increase in the use of cell phones. It has significantly added to the rapidly increasing EMF smog, an unprecedented type of pollution consisting of radiation in the environment, thereby prompting the scientists to study the effects on humans. However, not many studies have been conducted to explore the effects of cell phone EMFr on growth and biochemical changes in plants. We investigated whether EMFr from cell phones inhibit growth of Vigna radiata (mung bean) through induction of conventional stress responses. Effects of cell phone EMFr (power density: 8.55 microW cm(-2); 900 MHz band width; for 1/2, 1, 2, and 4 h) were determined by measuring the generation of reactive oxygen species (ROS) in terms of malondialdehyde and hydrogen peroxide (H(2)O(2)) content, root oxidizability and changes in levels of antioxidant enzymes. Our results showed that cell phone EMFr significantly inhibited the germination (at > or =2 h), and radicle and plumule growths (> or =1 h) in mung bean in a time-dependent manner. Further, cell phone EMFr enhanced MDA content (indicating lipid peroxidation), and increased H(2)O(2) accumulation and root oxidizability in mung bean roots, thereby inducing oxidative stress and cellular damage. In response to EMFr, there was a significant upregulation in the activities of scavenging enzymes, such as superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases, catalases and glutathione reductases, in mung bean roots. The study concluded that cell phone EMFr inhibit root growth of mung bean by inducing ROS-generated oxidative stress despite increased activities of antioxidant enzymes.

  8. Interleukin-13 inhibits inducible nitric oxide synthase expression in human mesangial cells.

    PubMed Central

    Saura, M; Martínez-Dalmau, R; Minty, A; Pérez-Sala, D; Lamas, S

    1996-01-01

    The synthesis of nitric oxide in inflammatory situations requires the expression of an inducible isoform of nitric oxide synthase (iNOS). Human mesangial cells (HMC) express an iNOS enzyme after exposure to multiple co-stimuli. In this study we have observed that while tumour necrosis factor-alpha, interleukin (IL)-1 beta, interferon-gamma and bacterial lipopolysaccharide (LPS) were unable to significantly induce NO synthesis when used alone, they induced an evident stimulation of NO synthesis when used in various combinations. A mixture of the three cytokines (CM) and LPS resulted in a 10-15-fold stimulation of NO synthesis over control values which started to be significant after 16 h. The addition of IL-13, a cytokine with anti-inflammatory properties, inhibited CM/LPS-induced NO synthesis in a concentration-dependent manner. A marked inhibitory effect (60-65%) could be observed when HMC were treated with IL-13 (10 ng/ml) 24 h before, at the same time as, or even 4 h after the addition of CM/LPS. This inhibitory effect was still significant (25%) when IL-13 was added 16 h after CM/LPS. Northern analysis showed that IL-13-mediated iNOS inhibition was closely correlated with the suppression of iNOS mRNA expression. These results identify IL-13 as a powerful regulatory tool for the inhibition of NO synthesis in human cells, a property which may be pathophysiologically relevant in NO-related inflammatory processes. PMID:8573104

  9. 4-Methylcoumarin Derivatives Inhibit Human Neutrophil Oxidative Metabolism and Elastase Activity

    PubMed Central

    Fuzissaki, Carolina N.; Andrade, Micássio F.; Azzolini, Ana Elisa C.S.; Taleb-Contini, Silvia H.; Vermelho, Roberta B.; Lopes, João Luis C.; Lucisano-Valim, Yara Maria

    2013-01-01

    Abstract Increased neutrophil activation significantly contributes to the tissue damage in inflammatory illnesses; this phenomenon has motivated the search for new compounds to modulate their effector functions. Coumarins are natural products that are widely consumed in the human diet. We have evaluated the antioxidant and immunomodulator potential of five 4-methylcoumarin derivatives. We found that the 4-methylcoumarin derivatives inhibited the generation of reactive oxygen species by human neutrophils triggered by serum-opsonized zymosan or phorbol-12-myristate-13-acetate; this inhibition occurred in a concentration-dependent manner, as revealed by lucigenin- and luminol-enhanced chemiluminescence assays. Cytotoxicity did not mediate this inhibitory effect. The 7,8-dihydroxy-4-methylcoumarin suppressed the neutrophil oxidative metabolism more effectively than the 6,7- and 5,7-dihydroxy-4-methylcoumarins, but the 5,7- and 7,8-diacetoxy-4-methylcoumarins were less effective than their hydroxylated counterparts. An analysis of the biochemical pathways suggested that the 6,7- and 7,8-dihydroxy-4-methylcoumarins inhibit the protein kinase C-mediated signaling pathway, but 5,7-dihydroxy-4-methylcoumarin, as well as 5,7- and 7,8-diacetoxy-4-methylcoumarins do not significantly interfere in this pathway of the activation of the human neutrophil oxidative metabolism. The 4-methylcoumarin derivatives bearing the catechol group suppressed the elastase and myeloperoxidase activity and reduced the 1,1-diphenyl-2-picrylhydrazyl free radical the most strongly. Interestingly, the 5,7-dihydroxy-4-methylcoumarin scavenged hypochlorous acid more effectively than the o-dihydroxy-substituted 4-methylcoumarin derivatives, and the diacetoxylated 4-methylcoumarin derivatives scavenged hypochlorous acid as effectively as the 7,8-dihydroxy-4-methylcoumarin. The significant influence of small structural modifications in the inhibitory potential of 4-methylcoumarin derivatives on the

  10. Curcumin attenuates endothelial cell oxidative stress injury through Notch signaling inhibition.

    PubMed

    Yang, Yang; Duan, Weixun; Liang, Zhenxin; Yi, Wei; Yan, Juanjuan; Wang, Ning; Li, Yue; Chen, Wensheng; Yu, Shiqiang; Jin, Zhenxiao; Yi, Dinghua

    2013-03-01

    Previous studies have demonstrated that Notch signaling pathway plays a regulatory role in cellular oxidative stress injury (OSI). In this study, our aim was to explore the role of the Notch signaling pathway in hydrogen peroxide (H(2)O(2))-induced OSI and the protective effect of curcumin during (H(2)O(2))-induced injury in human umbilical vein endothelial cells (HUVECs). DAPT, a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to study Notch activity. Further, HUVECs were exposed to H(2)O(2) in the absence or presence of curcumin. DAPT and Notch1 siRNA significantly inhibited OSI and the expression of Notch1 and Hes1. Curcumin conferred a protective effect on the HUVECs against H(2)O(2), which was evidenced by improved cell viability, adhesive ability and migratory ability and a decreased apoptotic index, decreased production of reactive oxygen species (ROS) and a reduction in several biochemical parameters. Immunofluorescence and Western blotting analyses demonstrated that H(2)O(2) treatment upregulated the expression of Notch1, Hes1, Caspase3, Bax and cytochrome c downregulated the expression of Bcl2, and treatment with curcumin reversed these effects. We demonstrated for the first time that the inhibition of Notch signaling pathway imparts a protective effect against endothelial OSI. The protective effects of curcumin against OSI are at least in part dependent on Notch1 inhibition.

  11. Wnt5a inhibits K(+) currents in hippocampal synapses through nitric oxide production.

    PubMed

    Parodi, Jorge; Montecinos-Oliva, Carla; Varas, Rodrigo; Alfaro, Iván E; Serrano, Felipe G; Varas-Godoy, Manuel; Muñoz, Francisco J; Cerpa, Waldo; Godoy, Juan A; Inestrosa, Nibaldo C

    2015-09-01

    Hippocampal synapses play a key role in memory and learning processes by inducing long-term potentiation and depression. Wnt signaling is essential in the development and maintenance of synapses via several mechanisms. We have previously found that Wnt5a induces the production of nitric oxide (NO), which modulates NMDA receptor expression in the postsynaptic regions of hippocampal neurons. Here, we report that Wnt5a selectively inhibits a voltage-gated K(+) current (Kv current) and increases synaptic activity in hippocampal slices. Further supporting a specific role for Wnt5a, the soluble Frizzled receptor protein (sFRP-2; a functional Wnt antagonist) fully inhibits the effects of Wnt5a. We additionally show that these responses to Wnt5a are mediated by activation of a ROR2 receptor and increased NO production because they are suppressed by the shRNA-mediated knockdown of ROR2 and by 7-nitroindazole, a specific inhibitor of neuronal NOS. Together, our results show that Wnt5a increases NO production by acting on ROR2 receptors, which in turn inhibit Kv currents. These results reveal a novel mechanism by which Wnt5a may regulate the excitability of hippocampal neurons.

  12. Human erythrocyte delta-aminolevulinate dehydratase inhibition by monosaccharides is not mediated by oxidation of enzyme sulfhydryl groups.

    PubMed

    Gabriel, D; Pivetta, L; Folmer, V; Soares, J C M; Augusti, G R; Nogueira, C W; Zeni, G; Rocha, J B T

    2005-08-01

    The heme pathway enzyme delta-aminolevulinate dehydratase is a good marker for oxidative stress and metal intoxication. This sulfhydryl enzyme is inhibited in such oxidative pathologies as lead, mercury and aluminum intoxication, exposure to selenium organic species and diabetes. Oxidative stress is a complicating factor in diabetes, inducing non-enzymatic glucose-mediated reactions that change protein structures and impair enzyme functions. We have studied the effects of high glucose, fructose and ribose concentrations on delta-ALA-D activity in vitro. These reducing sugars inhibited delta-ALA-D with efficacies in the order fructose=ribose>glucose. The possible mechanism of glucose inhibition was investigated using lysine, DTT, and t-butylamine. Oxidation of the enzyme's critical sulfhydryl groups was not involved because DTT had no effect. We concluded that high concentrations of reducing sugars or their autoxidation products inhibit delta-ALA-D by a mechanism not related to thiol oxidation. Also, we are not able to demonstrate that the formation of a Schiff base with the critical lysine residue of the enzyme is involved in the inhibition of delta-ALA-D by hexoses.

  13. Metal inhibition on the reactivity of manganese dioxide toward organic contaminant oxidation in relation to metal adsorption and ionic potential.

    PubMed

    Jiang, Jing; Wang, Zhuopu; Chen, Yang; He, Anfei; Li, Jianliang; Sheng, G Daniel

    2017-03-01

    Coexisting metal ions may significantly inhibit the oxidative reactivity of manganese oxides toward organic contaminants in metal-organic multi-pollutant waters. While the metal inhibition on the oxidation of organic contaminants by manganese oxides has previously been reported, the extent of the inhibition in relation to metal properties has not been established. Six alkali, alkaline, and transition metals, as well as two testing metals were evaluated for their abilities to inhibit the reactivity of birnessite. Regardless of the pathways of phenol and diuron oxidation (polymerization vs. breakdown), the extent of metal inhibition depended mainly on the metal itself and its concentration. The observed metal inhibition efficiency followed the order of Mn(2+) > Co(2+) > Cu(2+) > Al(3+) > Mg(2+) > K(+), consistent with metal adsorption on birnessite. The first-order organic oxidation rate constant (kobs) was linearly negatively correlated with metal adsorption (qe) on birnessite. These observations demonstrated that the metal inhibition efficiency was determined by metal adsorption on birnessite. The slopes of the kobs-qe varied among metals and followed the order of K(+) > Ca(2+) > Mg(2+) > Mn(2+) > Cd(2+) > Co(2+) > Cu(2+) > Al(3+). These slopes defined intrinsic inhibitory abilities of metals. As metals were adsorbed hydrated on birnessite, the intrinsic inhibitory ability was significantly linearly correlated with ionic potentials of metals, leading to a single straight line. Metals with multiple d electrons in the outermost orbit with polarizing energy that promotes hydrolysis sat slightly below the line, and vice versa.

  14. Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress.

    PubMed

    Wang, Lintao; Huang, Zhouqing; Huang, Weijian; Chen, Xuemei; Shan, Peiren; Zhong, Peng; Khan, Zia; Wang, Jingying; Fang, Qilu; Liang, Guang; Wang, Yi

    2017-04-04

    Atherosclerosis is a progressive disease leading to loss of vascular homeostasis and entails fibrosis, macrophage foam cell formation, and smooth muscle cell proliferation. Recent studies have reported that epidermal growth factor receptor (EGFR) is involved vascular pathophysiology and in the regulation of oxidative stress in macrophages. Although, oxidative stress and inflammation play a critical role in the development of atherosclerosis, the underlying mechanisms are complex and not completely understood. In the present study, we have elucidated the role of EGFR in high-fat diet-induced atherosclerosis in apolipoprotein E null mice. We show increased EGFR phosphorylation and activity in atherosclerotic lesion development. EGFR inhibition prevented oxidative stress, macrophage infiltration, induction of pro-inflammatory cytokines, and SMC proliferation within the lesions. We further show that EGFR is activated through toll-like receptor 4. Disruption of toll-like receptor 4 or the EGFR pathway led to reduced inflammatory activity and foam cell formation. These studies provide evidence that EGFR plays a key role on the pathogenesis of atherosclerosis, and suggests that EGFR may be a potential therapeutic target in the prevention of atherosclerosis development.

  15. Inhibition of cytoskeletal protein carbonylation may protect against oxidative damage in traumatic brain injury

    PubMed Central

    Zhang, Qiusheng; Zhang, Meng; Huang, Xianjian; Liu, Xiaojia; Li, Weiping

    2016-01-01

    Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates protracted neuronal dysfunction and remodeling. Cytoskeletal proteins are known to be carbonylated under oxidative stress; however, the complex molecular and cellular mechanisms of cytoskeletal protein carbonylation remain poorly understood. In the present study, the expression levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were investigated in PC12 cells treated with H2O2. Western blot analysis was used to monitor the carbonylation levels of β-actin and β-tubulin. The results indicated that oxidative stress was increased in PC12 cells that were treated with H2O2 for 24 or 48 h. In addition, increased carbonylation levels of β-actin and β-tubulin were detected in H2O2-treated cells. However, these carbonylation levels were reduced by pretreatment with aminoguanidine, a type of reactive carbonyl species chelating agent, and a similar trend was observed following overexpression of proteasome β5 via transgenic technology. In conclusion, the present study results suggested that the development of TBI may cause carbonylation of cytoskeletal proteins, which would then undermine the stability of cytoskeletal proteins. Thus, the development of TBI may be improved via the inhibition of cytoskeletal protein carbonylation. PMID:28101189

  16. Oxidized Phospholipids Inhibit the Formation of Cholesterol-Dependent Plasma Membrane Nanoplatforms

    PubMed Central

    Brameshuber, Mario; Sevcsik, Eva; Rossboth, Benedikt K.; Manner, Christina; Deigner, Hans-Peter; Peksel, Begüm; Péter, Mária; Török, Zsolt; Hermetter, Albin; Schütz, Gerhard J.

    2016-01-01

    We previously developed a single-molecule microscopy method termed TOCCSL (thinning out clusters while conserving stoichiometry of labeling), which allows for direct imaging of stable nanoscopic platforms with raft-like properties diffusing in the plasma membrane. As a consensus raft marker, we chose monomeric GFP linked via a glycosylphosphatidylinositol (GPI) anchor to the cell membrane (mGFP-GPI). With this probe, we previously observed cholesterol-dependent homo-association to nanoplatforms diffusing in the plasma membrane of live CHO cells. Here, we report the release of this homo-association upon addition of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) or 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, two oxidized phospholipids (oxPLs) that are typically present in oxidatively modified low-density lipoprotein. We found a dose-response relationship for mGFP-GPI nanoplatform disintegration upon addition of POVPC, correlating with the signal of the apoptosis marker Annexin V-Cy3. Similar concentrations of lysolipid showed no effect, indicating that the observed phenomena were not linked to properties of the lipid bilayer itself. Inhibition of acid sphingomyelinase by NB-19 before addition of POVPC completely abolished nanoplatform disintegration by oxPLs. In conclusion, we were able to determine how oxidized lipid species disrupt mGFP-GPI nanoplatforms in the plasma membrane. Our results favor an indirect mechanism involving acid sphingomyelinase activity rather than a direct interaction of oxPLs with nanoplatform constituents. PMID:26745423

  17. Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.

    PubMed

    Baila, Bulin; Ohno, Yasushi; Nagamoto, Hisashi; Kotosai, Kounori; Yabuuchi, Youichi; Funaguchi, Norihiko; Ito, Fumitaka; Endo, Junki; Mori, Hidenori; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi; Minatoguchi, Shinya

    2012-01-01

    Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

  18. Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

    NASA Technical Reports Server (NTRS)

    Pizza, F. X.; Hernandez, I. J.; Tidball, J. G.

    1998-01-01

    The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

  19. Inhibition of microbiological sulfide oxidation by methanethiol and dimethyl polysulfides at natron-alkaline conditions.

    PubMed

    van den Bosch, Pim L F; de Graaff, Marco; Fortuny-Picornell, Marc; van Leerdam, Robin C; Janssen, Albert J H

    2009-06-01

    To avoid problems related to the discharge of sulfidic spent caustics, a biotechnological process is developed for the treatment of gases containing both hydrogen sulfide and methanethiol. The process operates at natron-alkaline conditions (>1 mol L(-1) of sodium- and potassium carbonates and a pH of 8.5-10) to enable the treatment of gases with a high partial CO(2) pressure. In the process, methanethiol reacts with biologically produced sulfur particles to form a complex mixture predominantly consisting of inorganic polysulfides, dimethyl disulfide (DMDS), and dimethyl trisulfide (DMTS). The effect of these organic sulfur compounds on the biological oxidation of sulfide to elemental sulfur was studied with natron-alkaliphilic bacteria belonging to the genus Thioalkalivibrio. Biological oxidation rates were reduced by 50% at 0.05 mM methanethiol, while for DMDS and DMTS, this was estimated to occur at 1.5 and 1.0 mM, respectively. The inhibiting effect of methanethiol on biological sulfide oxidation diminished due to its reaction with biologically produced sulfur particles. This reaction increases the feasibility of biotechnological treatment of gases containing both hydrogen sulfide and methanethiol at natron-alkaline conditions.

  20. iNOS inhibition improves autonomic dysfunction and oxidative status in hypertensive obese rats.

    PubMed

    da Cunha, Natalia Veronez; Lopes, Fernanda Novi Cortegoso; Panis, Carolina; Cecchini, Rubens; Pinge-Filho, Phileno; Martins-Pinge, Marli Cardoso

    2017-01-01

    It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE2). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE2 was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.

  1. Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress

    PubMed Central

    Wang, Lintao; Huang, Zhouqing; Huang, Weijian; Chen, Xuemei; Shan, Peiren; Zhong, Peng; Khan, Zia; Wang, Jingying; Fang, Qilu; Liang, Guang; Wang, Yi

    2017-01-01

    Atherosclerosis is a progressive disease leading to loss of vascular homeostasis and entails fibrosis, macrophage foam cell formation, and smooth muscle cell proliferation. Recent studies have reported that epidermal growth factor receptor (EGFR) is involved vascular pathophysiology and in the regulation of oxidative stress in macrophages. Although, oxidative stress and inflammation play a critical role in the development of atherosclerosis, the underlying mechanisms are complex and not completely understood. In the present study, we have elucidated the role of EGFR in high-fat diet-induced atherosclerosis in apolipoprotein E null mice. We show increased EGFR phosphorylation and activity in atherosclerotic lesion development. EGFR inhibition prevented oxidative stress, macrophage infiltration, induction of pro-inflammatory cytokines, and SMC proliferation within the lesions. We further show that EGFR is activated through toll-like receptor 4. Disruption of toll-like receptor 4 or the EGFR pathway led to reduced inflammatory activity and foam cell formation. These studies provide evidence that EGFR plays a key role on the pathogenesis of atherosclerosis, and suggests that EGFR may be a potential therapeutic target in the prevention of atherosclerosis development. PMID:28374780

  2. Nanocomposite of p-type conductive polymer/functionalized graphene oxide nanosheets as novel and hybrid electrodes for highly capacitive pseudocapacitors.

    PubMed

    Ehsani, A; Mohammad Shiri, H; Kowsari, E; Safari, R; Torabian, J; Kazemi, S

    2016-09-15

    An effective approach for increasing the life cycle of poly ortho aminophenol (POAP) as a p-type conductive polymers is combining conventional conductive polymers and nanomaterials to fabricate hybrid electrodes. In this paper, functionalized graphene oxide (FGO) has first been synthesized using a chemical approach. Hybrid POAP/FGO films have then been fabricated by POAP electropolymerization in the presence of FGO nanoparticles as active electrodes for electrochemical supercapacitors. Based on the atomic scale study results, it seems that H3PO4(-) oxygen atoms and terminal pyridine ring nitrogen atoms play a crucial role in the intramolecular charge and energy transfer in the FGO molecular systems. Theoretical studies, surface and electrochemical analyses have been used for characterization of POAP/FGO composite films. Different electrochemical methods including galvanostatic charge discharge experiments, cyclic voltammetry and electrochemical impedance spectroscopy have been applied to study the system performance. This work introduces new nanocomposite materials for electrochemical redox capacitors with such advantages as the ease of synthesis, high active surface area and stability in an aqueous electrolyte.

  3. Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide.

    PubMed

    Kwon, N S; Stuehr, D J; Nathan, C F

    1991-10-01

    Macrophage-derived nitric oxide (NO) is cytostatic to tumor cells and microbial pathogens. We tested whether one molecular target for the cytostatic action of NO may be ribonucleotide reductase (RR), a rate-limiting enzyme in DNA synthesis. In a concentration-dependent manner, NO gas and lysates of activated macrophages that generated comparable amounts of NO led to the same degree of inhibition of partially purified RR from L1210 mouse lymphoma cells. Lysates from nonactivated macrophages, which do not produce NO, were noninhibitory. With lysates from activated macrophages, RR was protected by omitting L-arginine or by adding the NO synthase inhibitors diphenyleneiodonium, N omega-methyl-L-arginine, or N omega-amino-L-arginine. L-Arginine, but not D-arginine, abolished the protective effect of N omega-amino-L-arginine. The prototypic pharmacologic inhibitor of RR is hydroxyurea. Its structural resemblance to N omega-hydroxy-L-arginine, a reaction intermediate of NO synthase, prompted us to test if hydroxyurea can generate NO. In the presence of H2O2 and CuSO4, hydroxyurea produced NO2-/NO3-, aerobic reaction products of NO. Addition of morpholine blocked NO2-/NO3- generation from hydroxyurea and led to formation of nitrosomorpholine, as detected by gas chromatography/mass spectrometry. Thus, hydroxyurea can produce an NO-like, nitrosating rectant. L1210 cell DNA synthesis was inhibited completely by activated macrophages or by hydroxyurea, and was partially restored to the same degree in both settings by providing deoxyribonucleosides to bypass the block in RR. Thus, both NO gas and NO generated by activated macrophage lysates inhibit tumor cell RR. The RR inhibitor hydroxyurea can also generate an NO-like species. Similar, partial restoration of tumor cell DNA synthesis by deoxyribonucleosides in the presence of activated macrophages or hydroxyurea suggests that cytostasis by activated macrophages and by hydroxyurea has comparable mechanisms, including, but

  4. Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity.

    PubMed

    Yamauchi, Mika; Tsuruma, Kazuhiro; Imai, Shunsuke; Nakanishi, Tomohiro; Umigai, Naofumi; Shimazawa, Masamitsu; Hara, Hideaki

    2011-01-10

    Crocetin is a carotenoid that is the aglicone of crocin, which are found in saffron stigmas (Crocus sativus L.) and gardenia fruit (Gardenia jasminoides Ellis). In this study, we investigated the effects of crocetin on retinal damage. To examine whether crocetin affects stress pathways, we investigated intracellular oxidation induced by reactive oxygen species, expression of endoplasmic reticulum (ER) stress-related proteins, disruption of the mitochondrial membrane potential (ΔΨ(m)), and caspases activation. In vitro, we employed cultured retinal ganglion cells (RGC-5, a mouse ganglion cell-line transformed using E1A virus). Cell damage was induced by tunicamycin or hydrogen peroxide (H(2)O(2)) exposure. Crocetin at a concentration of 3μM showed the inhibitory effect of 50-60% against tunicamycin- and H(2)O(2)-induced cell death and inhibited increase in caspase-3 and -9 activity. Moreover, crocetin inhibited the enzymatic activity of caspase-9 in a cell-free system. In vivo, retinal damage in mice was induced by exposure to white light at 8000lx for 3h after dark adaptation. Photoreceptor damage was evaluated by measuring the outer nuclear layer thickness at 5days after light exposure and recording the electroretinogram (ERG). Retinal cell damage was also detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at 48h after light exposure. Crocetin at 100mg/kg, p.o. significantly inhibited photoreceptor degeneration and retinal dysfunction and halved the expression of TUNEL-positive cells. These results indicate that crocetin has protective effects against retinal damage in vitro and in vivo, suggesting that the mechanism may inhibit increase in caspase-3 and -9 activities after retinal damage.

  5. Negative capacitance for ultra-low power computing

    NASA Astrophysics Data System (ADS)

    Khan, Asif Islam

    Owing to the fundamental physics of the Boltzmann distribution, the ever-increasing power dissipation in nanoscale transistors threatens an end to the almost-four-decade-old cadence of continued performance improvement in complementary metal-oxide-semiconductor (CMOS) technology. It is now agreed that the introduction of new physics into the operation of field-effect transistors---in other words, "reinventing the transistor'"--- is required to avert such a bottleneck. In this dissertation, we present the experimental demonstration of a novel physical phenomenon, called the negative capacitance effect in ferroelectric oxides, which could dramatically reduce power dissipation in nanoscale transistors. It was theoretically proposed in 2008 that by introducing a ferroelectric negative capacitance material into the gate oxide of a metal-oxide-semiconductor field-effect transistor (MOSFET), the subthreshold slope could be reduced below the fundamental Boltzmann limit of 60 mV/dec, which, in turn, could arbitrarily lower the power supply voltage and the power dissipation. The research presented in this dissertation establishes the theoretical concept of ferroelectric negative capacitance as an experimentally verified fact. The main results presented in this dissertation are threefold. To start, we present the first direct measurement of negative capacitance in isolated, single crystalline, epitaxially grown thin film capacitors of ferroelectric Pb(Zr0.2Ti0.8)O3. By constructing a simple resistor-ferroelectric capacitor series circuit, we show that, during ferroelectric switching, the ferroelectric voltage decreases, while the stored charge in it increases, which directly shows a negative slope in the charge-voltage characteristics of a ferroelectric capacitor. Such a situation is completely opposite to what would be observed in a regular resistor-positive capacitor series circuit. This measurement could serve as a canonical test for negative capacitance in any novel

  6. Silicon-Neuron Junction: Capacitive Stimulation of an Individual Neuron on a Silicon Chip

    NASA Astrophysics Data System (ADS)

    Fromherz, Peter; Stett, Alfred

    1995-08-01

    An identified nerve cell of the leech is attached to a planar silicon microstructure of p-doped silicon covered by a thin layer of insulating silicon oxide. A voltage step, applied between silicon and electrolyte, induces a capacitive transient in the cell which elicits an action potential. The capacitive extracellular stimulation is described by an equivalent electrical four-pole.

  7. Shielded capacitive electrode

    DOEpatents

    Kireeff Covo, Michel

    2013-07-09

    A device is described, which is sensitive to electric fields, but is insensitive to stray electrons/ions and unlike a bare, exposed conductor, it measures capacitively coupled current while rejecting currents due to charged particle collected or emitted. A charged particle beam establishes an electric field inside the beam pipe. A grounded metallic box with an aperture is placed in a drift region near the beam tube radius. The produced electric field that crosses the aperture generates a fringe field that terminates in the back surface of the front of the box and induces an image charge. An electrode is placed inside the grounded box and near the aperture, where the fringe fields terminate, in order to couple with the beam. The electrode is negatively biased to suppress collection of electrons and is protected behind the front of the box, so the beam halo cannot directly hit the electrode and produce electrons. The measured signal shows the net potential (positive ion beam plus negative electrons) variation with time, as it shall be observed from the beam pipe wall.

  8. Capacitive deionization system

    SciTech Connect

    Richardson, J. H., LLNL

    1996-10-01

    The new capacitive deionization system (CDI) removes ions, contaminants impurities from water and other aqueous process streams, and further selectively places the removed ions back into solution during regeneration. It provides a separation process that does not utilize chemical regeneration processes, and thus significantly reduces or completely eliminates secondary wastes associated with the operation of ion exchange resins. In the CDI, electrolyte flows in open channels formed between adjacent electrodes, and consequently the pressure drop is much lower than conventional separation processes. The fluid flow can be gravity fed through these open channels, and does not require membranes. This feature represents a significant advantage over the conventional reverse osmosis systems which include water permeable cellulose acetate membranes, and over the electrodialysis systems which require expensive and exotic ion exchange membranes. The CDI is adaptable for use in a wide variety of commercial applications, including domestic water softening, industrial water softening, waste water purification, sea water desalination, treatment of nuclear and aqueous wastes, treatment of boiler water in nuclear and fossil power plants, production of high-purity water for semiconductor processing, and removal of salt from water for agricultural irrigation. CDI accomplishes this removal of impurities by a variety of mechanisms, but predominantly by electrostatic removal of organic and inorganic ions from water or any other dielectric solvent.

  9. Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression.

    PubMed

    Saitoh, Yasukazu; Okayasu, Hajime; Xiao, Li; Harata, Yoshikazu; Miwa, Nobuhiko

    2008-01-01

    The properties and effects of neutral pH hydrogen-enriched electrolyzed water (NHE water) on tumor cells were examined. NHE water diminished hydroxyl radicals as demonstrated by ESR in a cell-free system. Human tongue carcinoma cells HSC-4 were inhibited for either colony formation efficiencies or colony sizes by NHE water without significant inhibition to normal human tongue epithelial-like cells DOK. Furthermore, NHE water caused growth inhibition, cell degeneration, and inhibition of invasion through the reconstituted basement membrane to human fibrosarcoma cells HT-1080. Intracellular oxidants such as hydroperoxides and hydrogen peroxides were scavenged in HSC-4 or HT-1080 cells by NHE water. In the human oral cavity, a dissolved hydrogen concentrations (DH) of NHE water was drastically declined from 1.1 to 0.5 ppm, but settled to 0.3-0.4 ppm until 180 s, upon static holding without gargling. Thus, NHE water was shown to achieve tumor-preferential growth inhibition and tumor invasion together with scavenging of intracellular oxidants, and is expected as a preventive material against tumor progression and invasion.

  10. Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.

    PubMed

    Das Gupta, Soumyasri; So, Jae Young; Wall, Brian; Wahler, Joseph; Smolarek, Amanda K; Sae-Tan, Sudathip; Soewono, Kelvin Y; Yu, Haixiang; Lee, Mao-Jung; Thomas, Paul E; Yang, Chung S; Suh, Nanjoo

    2015-09-01

    Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17β-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer.

  11. Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

    SciTech Connect

    Chen, Jing-Hsien; Tsai, Chia-Wen; Wang, Chi-Ping; Lin, Hui-Hsuan

    2013-10-15

    Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu{sup 2+}-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression.

  12. Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress.

    PubMed

    Lee, Joo Hyoung; Kang, Minsung; Wang, Hong; Naik, Gurudatta; Mobley, James A; Sonpavde, Guru; Garvey, W Timothy; Darley-Usmar, Victor M; Ponnazhagan, Selvarangan

    2017-04-01

    Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling. This reversal after ES treatment significantly decreased PCa cell proliferation through down-regulation of GR and up-regulation of manganese superoxide dismutase and reduced glutathione levels. Proteome and biochemical analyses of ES-treated PCa cells further indicated a significant up-regulation of enzymes in the major reactive oxygen species (ROS) scavenging machinery, including catalase, glutathione synthetase, glutathione reductase, NADPH-cytochrome P450 reductase, biliverdin reductase, and thioredoxin reductase, resulting in a concomitant reduction of intracellular ROS. ES further augmented the antioxidant system through up-regulation of glucose influx, the pentose phosphate pathway, and NAD salvaging pathways. This shift in cancer cell redox homeostasis by ES significantly decreased the effect of protumorigenic oxidative machinery on androgen-independent PCa growth, suggesting that ES can suppress GR-induced resistant phenotype upon AR antagonism and that the dual targeting action of ES on AR and GR can be further translated to PCa therapy.-Lee, J. H., Kang, M., Wang, H., Naik, G., Mobley, J. A., Sonpavde, G., Garvey, W. T., Darley-Usmar, V. M., Ponnazhagan, S. Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress.

  13. Increased uptake of oxidized LDL by macrophages from type 2 diabetics is inhibited by polyamines.

    PubMed

    Balderas, Francisco L; Quezada-Larios, Marina; García Latorre, Ethel Awilda; Méndez, José D

    2016-02-01

    The aim of this study was to evaluate the effect of polyamines putrescine, spermidine and spermine on human LDL oxidation and to assess the ability of macrophages derived from type 2 diabetic patients to uptake oxLDL. Polyamine effect was compared with α-tocopherol. Four healthy subjects and eight type 2 diabetic patients were included in this study. To characterize type 2 diabetic patients and non-diabetic subjects, laboratory test were carried out. Glucose, glycated haemoglobin (HbA1C), triglycerides, low (LDL) and high density lipoproteins (HDL) and serum lipid peroxidation were measured in blood. The study was performed in three stages. For each stage, ten experimental conditions comparing the effect of polyamines with α-tocopherol (10μM solutions) on LDL oxidation and the uptake of oxLDL by macrophages were analyzed. MDA concentration was found to be significantly higher in type 2 diabetic patients compared to healthy subjects (5.6±0.58 vs. 2.66±0.31μM MDA, respectively, (P<0.05)). Percent of macrophages containing oxLDL was determined by means of red oil staining. The uptake of oxLDL by macrophages derived from diabetic patients was clear. The uptake of oxLDL was inhibited when the oxidation was prevented by polyamines or α-tocopherol. Spermine showed high antioxidant capacity (96.67±1.53% vs. 25.67±2.30%) compared to α-tocopherol (96.67±1.53% vs. 47.00±7.20%) at the concentration tested. In conclusion, polyamines especially spermine, has a potent antioxidant effect compared to α-tocopherol on human LDL oxidation, followed by spermidine and putrescine. The results have clinical relevance in the diabetic complications and add knowledge on the role of polyamines as natural antioxidants. This research is not a clinical evaluation rather a functional analysis utilizing clinical samples.

  14. Capacitation inducers act through diverse intracellular mechanisms in cryopreserved bovine sperm.

    PubMed

    Breininger, E; Cetica, P D; Beconi, M T

    2010-10-01

    The effect of various capacitation inducers, i.e. heparin, superoxide anion, bicarbonate, adenosine, and caffeine, and their role in intracellular mechanisms involved in capacitation, were studied in cryopreserved bovine sperm. Capacitation was determined by epifluorescence chlortetracycline, protein tyrosine phosphorylation, and the ability of capacitated sperm to undergo an acrosome reaction and fertilize in vitro matured oocytes. Participation of membrane adenylate cyclase and protein kinases (protein kinase A, protein kinase C, and protein tyrosine kinase) was evaluated indirectly (with specific inhibitors). Involvement of reactive oxygen species (ROS) was determined with scavengers of superoxide anion, hydrogen peroxide, or nitric oxide. Percentages of capacitated (27-29%) and acrosome-reacted sperm (23-26%) did not differ (P > 0.05) among various capacitation inducers. Significantly higher rates of IVF were obtained with heparin (43%) or bicarbonate plus caffeine (45%), when compared with control samples (17%). Adding the membrane adenylate cyclase inhibitor diminished capacitation rates with heparin (8%) or adenosine (10%). There was differential protein kinase participation in response to inducers; protein kinase inhibitors diminished cleavage rates in heparin-capacitated sperm relative to controls. There were differences between and within the studied inducers in protein tyrosine phosphorylation patterns. We inferred that capacitation in cryopreserved bovine sperm was promoted through diverse pathways. Mechanisms triggered by heparin, or caffeine plus bicarbonate-induced capacitation, involved activation of intracellular pathways to optimize fertilizing capability of cryopreserved bovine sperm.

  15. Miniature electrometer preamplifier effectively compensates for input capacitance

    NASA Technical Reports Server (NTRS)

    Burrous, C. N.; Deboo, G. J.

    1966-01-01

    Negative capacitance preamplifier using a dual MOS /Metal Oxide Silicon/ transistor in conjunction with bipolar transistors is used with intracellular microelectrodes in recording bioelectric potentials. Applications would include use as a pickup plate video amplifier in storage tube tests and for pH and ionization chamber measurements.

  16. Nitric oxide signaling pathway activation inhibits the immune escape of pancreatic carcinoma cells

    PubMed Central

    LU, YEBIN; HU, JUANJUAN; SUN, WEIJIA; DUAN, XIAOHUI; CHEN, XIONG

    2014-01-01

    The aim of the present study was to investigate the effect of the nitric oxide signaling pathway on immune escape; thus, a tumorigenesis model was established using nude mice. The mice were inoculated with pancreatic carcinoma cells and divided into two groups, a glyceryl trinitrate (GTN) and a placebo group. When tumor volumes reached 150 mm3, the mice in the GTN group were treated with GTN transdermal patches (dose, 7.3 μg/h) while the mice in the placebo group were administered untreated patches. Following treatment, the tumor volume was recorded every 3–4 days and after 28 days, the tumors were analyzed. The results indicated that GTN treatment may reduce the levels of soluble major histocompatibility complex class I chain-related molecules, and natural killer group 2 member D, as well as inhibiting tumor growth. PMID:25364398

  17. Lignans from Arctium lappa and their inhibition of LPS-induced nitric oxide production.

    PubMed

    Park, So Young; Hong, Seong Su; Han, Xiang Hua; Hwang, Ji Sang; Lee, Dongho; Ro, Jai Seup; Hwang, Bang Yeon

    2007-01-01

    A new butyrolactone sesquilignan, isolappaol C (1), together with four known lignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5), were isolated from the methanolic extract of the seeds from the Arctium lappa plant. The structure of isolappaol C (1) was determined by spectral analysis including 1D- and 2D-NMR. All the isolates were evaluated for their inhibitory effects on the LPS-induced nitric oxide production using murine macrophage RAW264.7 cells. Lappaol F (4) and diarctigenin (5) strongly inhibited NO production in the LPS-stimulated RAW264.7 cells with IC(50) values of 9.5 and 9.6 microM, respectively.

  18. Inhibition effect of graphene oxide on the catalytic activity of acetylcholinesterase enzyme.

    PubMed

    Wang, Yong; Gu, Yao; Ni, Yongnian; Kokot, Serge

    2015-11-01

    Variations in the enzyme activity of acetylcholinesterase (AChE) in the presence of the nano-material, graphene oxide (GO), were investigated with the use of molecular spectroscopy UV-visible and fluorescence methods. From these studies, important kinetic parameters of the enzyme were extracted; these were the maximum reaction rate, Vm , and the Michaelis constant, Km . A comparison of these parameters indicated that GO inhibited the catalytic activity of the AChE because of the presence of the AChE-GO complex. The formation of this complex was confirmed with the use of fluorescence data, which was resolved with the use of the MCR-ALS chemometrics method. Furthermore, it was found that the resonance light-scattering (RLS) intensity of AChE changed in the presence of GO. On this basis, it was demonstrated that the relationship between AChE and GO was linear and such models were used for quantitative analyses of GO.

  19. Nitric oxide donors preferentially inhibit neuronally mediated rat gastric acid secretion.

    PubMed

    Barrachina, D; Calatayud, S; Esplugues, J; Whittle, B J; Moncada, S; Esplugues, J V

    1994-09-01

    Continuous i.v. infusion of the nitric oxide (NO) donors, S-nitroso-glutathione (10-50 micrograms kg-1 min-1) and S-nitroso-N-acetyl-penicillamine (10 micrograms kg-1 min-1) inhibited neuronally mediated gastric acid secretion, as induced by gastric distension (20 cm water) or i.v. bolus administration of 2-deoxy-D-glucose (150 mg kg-1) in the anaesthetized rat. By contrast, gastric acid responses to i.v. infusion of submaximal doses of pentagastrin (8 micrograms kg-1 h-1) or histamine (1 mg kg-1 h-1) were not influenced by these NO donors. These findings suggest that NO does not directly influence acid secretion in vivo but could play an inhibitory modulator role in neuronally mediated acid responses.

  20. Ethylenediamine Promotes Cu Nanowire Growth by Inhibiting Oxidation of Cu(111).

    PubMed

    Kim, Myung Jun; Flowers, Patrick F; Stewart, Ian E; Ye, Shengrong; Baek, Seungyeon; Kim, Jae Jeong; Wiley, Benjamin J

    2017-01-11

    The synthesis of metal nanostructures usually requires a capping agent that is generally thought to cause anisotropic growth by blocking the addition of atoms to specific crystal facets. This work uses a series of electrochemical measurements with a quartz crystal microbalance and single-crystal electrodes to elucidate the facet-selective chemistry occurring in the synthesis of Cu nanowires. Contrary to prevailing hypotheses, ethylenediamine, a so-called capping agent in the synthesis of Cu nanowires, causes anisotropic growth by increasing the rate of atomic addition to (111) facets at the end of a growing nanowire relative to (100) facets on the sides of a nanowire. Ethylenediamine increases the reduction rate of Cu(OH)2(-) on a Cu(111) surface relative to Cu(100) by selectively inhibiting the formation of Cu oxide on Cu(111). This work demonstrates how studying facet-selective electrochemistry can improve the understanding of the processes by which atoms assemble to form anisotropic metal nanostructures.

  1. Aqueous Extract of Dried Flower Buds of Syzygium aromaticum Inhibits Inflammation and Oxidative Stress

    PubMed Central

    Ahmad, Tasleem; Shinkafi, Tijjani Salihu; Routray, Indusmitha; Mahmood, Amena; Ali, Shakir

    2012-01-01

    This study reports the beneficial effect of aqueous extract of dried flower buds of Syzygium aromaticum (clove) in acute and chronic inflammation. Inflammation was induced in rats by injecting carrageenan in hind paw or implanting cotton pellet in the axilla. Administration of the extract (1 g/kg body weight) inhibited the formation of oedema induced by carrageenan and decreased granuloma in cotton pellet granuloma model. The extract, when compared with the disease control, is reported to decrease the elevated levels of succinate dehydrogenase (p<0.001), xanthine oxidase (p<0.05) and lipid peroxidation, and increase the activity of catalase (p<0.001) and glutathione peroxidase (p<0.01) in the two animal models. Potential role of xanthine oxidase in inflammation and the ability of the extract to alleviate oxidative stress and inflammation is discussed. The study advocates the use of aqueous extract, rather than the isolated bioactive principle for various reasons. PMID:24826043

  2. Substrate inhibition: Oxidation of D-sorbitol and D-mannitol by potassium periodate in alkaline medium

    NASA Astrophysics Data System (ADS)

    Lakshman Kumar, Y.; Venkata Nadh, R.; Radhakrishnamurti, P. S.

    2014-05-01

    In the oxidation of D-sorbitol and D-mannitol by potassium periodate in alkaline media, substrate inhibition was observed with both substrates, i.e., a decrease in the rate of the reaction was observed with an increase in the concentration of substrate. The substrate inhibition was attributed to the formation of stable complex between the substrate and periodate. The reactions were found to be first order in case of periodate and a positive fractional order with hydroxide ions. Arrhenius parameters were calculated for the oxidation of sorbitol and mannitol by potassium periodate in alkali media.

  3. Cisplatin inhibits the formation of a reactive intermediate during copper-catalyzed oxidation of amyloid β peptide.

    PubMed

    Walke, Gulshan R; Rapole, Srikanth; Kulkarni, Prasad P

    2014-10-06

    Cisplatin was studied for its effect on the copper-catalyzed oxidation of amyloid β (Aβ) peptide. The interaction of cisplatin with Aβ1-16 in the presence of Cu(II) was investigated using cyclic voltammetry and mass spectrometry. The positive shift in the E1/2 value of Aβ1-16-Cu(II) suggests that the interaction of cisplatin alters the copper-binding properties of Aβ1-16. The mass spectrometry data show complete inhibition of copper-catalyzed decarboxylation/deamination of the Asp1 residue of Aβ1-16, while there is a significant decrease in copper-catalyzed oxidation of Aβ1-16 in the presence of cisplatin. Overall, our results provide a novel mode by which cisplatin inhibits copper-catalyzed oxidation of Aβ. These findings may lead to the design of better platinum complexes to treat oxidative stress in Alzheimer's disease and other related neurological disorders.

  4. Effects of Selenium Yeast on Oxidative Stress, Growth Inhibition, and Apoptosis in Human Breast Cancer Cells.

    PubMed

    Guo, Chih-Hung; Hsia, Simon; Shih, Min-Yi; Hsieh, Fang-Chin; Chen, Pei-Chung

    2015-01-01

    Recent evidence suggests that selenium (Se) yeast may exhibit potential anti-cancer properties; whereas the precise mechanisms remain unknown. The present study was aimed at evaluating the effects of Se yeast on oxidative stress, growth inhibition, and apoptosis in human breast cancer cells. Treatments of ER-positive MCF-7 and triple-negative MDA-MB-231 cells with Se yeast (100, 750, and 1500 ng Se/mL), methylseleninic acid (MSA, 1500 ng Se/mL), or methylselenocysteine (MSC, 1500 ng Se/mL) at a time course experiment (at 24, 48, 72, and 96 h) were analyzed. Se yeast inhibited the growth of these cancer cells in a dose- and time-dependent manner. Compared with the same level of MSA, cancer cells exposure to Se yeast exhibited a lower growth-inhibitory response. The latter has also lower superoxide production and reduced antioxidant enzyme activities. Furthermore, MSA (1500 ng Se/mL)-exposed non-tumorigenic human mammary epithelial cells (HMEC) have a significant growth inhibitory effect, but not Se yeast and MSC. Compared with MSA, Se yeast resulted in a greater increase in the early apoptosis in MCF-7 cells as well as a lower proportion of early and late apoptosis in MDA-MB-231 cells. In addition, nuclear morphological changes and loss of mitochondrial membrane potential were observed. In conclusion, a dose of 100 to 1500 ng Se/mL of Se yeast can increase oxidative stress, and stimulate growth inhibitory effects and apoptosis induction in breast cancer cell lines, but does not affect non-tumorigenic cells.

  5. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    SciTech Connect

    Curtis, Brandon M.; Leix, Kyle Alexander; Ji, Yajing; Glaves, Richard Samuel Elliot; Ash, David E.; Mohanty, Dillip K.

    2014-07-18

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

  6. Inhibition of neutral sphingomyelinase decreases elevated levels of inducible nitric oxide synthase and apoptotic cell death in ocular hypertensive rats

    SciTech Connect

    Aslan, Mutay; Basaranlar, Goksun; Unal, Mustafa; Ciftcioglu, Akif; Derin, Narin; Mutus, Bulent

    2014-11-01

    Endoplasmic reticulum (ER) stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS2) have been implicated in the pathogenesis of neuronal retinal cell death in ocular hypertension. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression, hence this study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on retinal NOS2 levels, ER stress, apoptosis and visual evoked potentials (VEPs) in a rat model of elevated intraocular pressure (EIOP). NOS2 expression and retinal protein nitration were significantly greater in EIOP and significantly decreased with N-SMase inhibition. A significant increase was observed in retinal ER stress markers pPERK, CHOP and GRP78 in EIOP, which were not significantly altered by N-SMase inhibition. Retinal TUNEL staining showed increased apoptosis in all EIOP groups; however N-SMase inhibition significantly decreased the percent of apoptotic cells in EIOP. Caspase-3, -8 and -9 activities were significantly increased in EIOP and returned to baseline levels following N-SMase inhibition. Latencies of all VEP components were significantly prolonged in EIOP and shortened following N-SMase inhibition. Data confirm the role of nitrative injury in EIOP and highlight the protective effect of N-SMase inhibition in EIOP via down-regulation of NOS2 levels and nitrative stress. - Highlights: • Inhibition of N-SMase decreases NOS2 levels in ocular hypertension. • Inhibition of N-SMase decreases protein nitration in ocular hypertension. • Inhibition of N-SMase decreases caspase activation in ocular hypertension. • Inhibition of N-SMase decreases apoptosis in ocular hypertension.

  7. Nitric oxide inhibition of alcohol dehydrogenase in fresh-cut apples ( Malus domestica Borkh).

    PubMed

    Amissah, Joris Gerald Niilante; Hotchkiss, Joseph H; Watkins, Chris B

    2013-11-20

    The effects of nitric oxide (NO) and nitrite treatment on alcohol dehydrogenase activity and the shelf life of apple tissue were investigated. Fresh-cut apple slices were stored for 2 days at 6 °C in 0.25-1% NO (v/v, balance N2) or 100% N2 atmospheres. Slices were also treated with 1% NO or 2 mM sodium nitrite (NaNO2) for 20 min, stored for 6 weeks in 100% N2 at 6 °C, and analyzed for acetaldehyde, ethanol, and ethyl acetate accumulation, firmness, and color. Compared with N2 or deionized water controls, treatment with 1% NO or 2 mM NaNO2 inhibited ethanol accumulation, whereas that of acetaldehyde increased. Ethyl acetate accumulation was inhibited only by NO. Slice firmness was not affected by NO or NaNO2 treatment, but slices were darker than the untreated controls. NO and nitrite may extend the shelf life of fresh-cut produce with low concentrations of phenolic compounds.

  8. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

    PubMed Central

    Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka Sakari; Nejadnik, Hossein; Goodman, Stuart; Moseley, Michael; Coussens, Lisa Marie; Daldrup-Link, Heike Elisabeth

    2016-01-01

    Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied ‘off label’ to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies. PMID:27668795

  9. Environmental stress causes oxidative damage to plant mitochondria leading to inhibition of glycine decarboxylase.

    PubMed

    Taylor, Nicolas L; Day, David A; Millar, A Harvey

    2002-11-08

    A cytotoxic product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), rapidly inhibited glycine, malate/pyruvate, and 2-oxoglutarate-dependent O2 consumption by pea leaf mitochondria. Dose- and time-dependence of inhibition showed that glycine oxidation was the most severely affected with a K(0.5) of 30 microm. Several mitochondrial proteins containing lipoic acid moieties differentially lost their reactivity to a lipoic acid antibody following HNE treatment. The most dramatic loss of antigenicity was seen with the 17-kDa glycine decarboxylase complex (GDC) H-protein, which was correlated with the loss of glycine-dependent O2 consumption. Paraquat treatment of pea seedlings induced lipid peroxidation, which resulted in the rapid loss of glycine-dependent respiration and loss of H-protein reactivity with lipoic acid antibodies. Pea plants exposed to chilling and water deficit responded similarly. In contrast, the damage to other lipoic acid-containing mitochondrial enzymes was minor under these conditions. The implication of the acute sensitivity of glycine decarboxylase complex H-protein to lipid peroxidation products is discussed in the context of photorespiration and potential repair mechanisms in plant mitochondria.

  10. Retinoic acid inhibits inducible nitric oxide synthase expression in 3T3-L1 adipocytes.

    PubMed

    Yang, Jeong-Yeh; Koo, Bon-Sun; Kang, Mi-Kyung; Rho, Hye-Won; Sohn, Hee-Sook; Jhee, Eun-Chung; Park, Jin-Woo

    2002-11-30

    The present study was undertaken to explore whether retinoids, which are known to have immunomodulatory actions, could attenuate tumor necrosis factor-alpha (TNF)-stimulated inducible nitric oxide synthase (iNOS) expression in 3T3-L1 adipocytes. Adipocytes incubated with TNF induced dose- and time-dependent accumulation of nitrite in the culture medium through the iNOS induction as confirmed by Western blotting. Treatment of cells with TNF in the presence of all-trans-retinoic acid (RA) significantly decreased their ability to produce nitrite and iNOS induction. Both 13-cis- and all- trans-RA-induced suppression was dose-dependent, and all-trans-RA was somewhat potent than 13-cis-RA. The inhibitory effect of RA on TNF-induced iNOS induction was reversible, completely recovered after 2 days, and was exerted through the inhibition of NF-kappaB activation. TNF also suppressed the lipoprotein lipase (LPL) activity of 3T3-L1 adipocytes. RA could not reverse the TNF- induced LPL suppression at RA levels causing near complete inhibition of the TNF-induced NO production. These results indicate that RAs attenuate iNOS expression reversibly in TNF-stimulated 3T3-L1 adipocytes, and that the TNF-induced LPL suppression is not the result of NO overproduction.

  11. The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production

    PubMed Central

    Bhat, Khalid Hussain; Srivastava, Shruti; Kotturu, Sandeep Kumar; Ghosh, Sudip; Mukhopadhyay, Sangita

    2017-01-01

    Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal. PPE2 was translocated into the macrophage nucleus via the classical importin α/β pathway where it interacted with a GATA-binding site overlapping with the TATA box of inos promoter and inhibited NO production. PPE2 prolonged intracellular survival of a surrogate bacterium M. smegmatis in vitro as well as in vivo. This information are likely to improve our knowledge of host-pathogen interactions during M. tuberculosis infection which is crucial for designing effective anti-TB therapeutics. PMID:28071726

  12. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka Sakari; Nejadnik, Hossein; Goodman, Stuart; Moseley, Michael; Coussens, Lisa Marie; Daldrup-Link, Heike Elisabeth

    2016-11-01

    Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

  13. Asbestos induces nitric oxide synthesis in mesothelioma cells via Rho signaling inhibition.

    PubMed

    Riganti, Chiara; Orecchia, Sara; Silvagno, Francesca; Pescarmona, Gianpiero; Betta, Pier Giacomo; Gazzano, Elena; Aldieri, Elisabetta; Ghigo, Dario; Bosia, Amalia

    2007-06-01

    We have observed that in three human malignant mesothelioma cell lines, crocidolite asbestos induced the activation of the transcription factor NF-kappaB and the synthesis of nitric oxide (NO) by inhibiting the RhoA signaling pathway. The incubation with crocidolite decreased the level of GTP-bound RhoA and the activity of Rho-dependent kinase, and induced the activation of Akt/PKB and IkBalpha kinase, leading to the nuclear translocation of NF-kappaB. The effects of crocidolite fibers on NF-kappaB activation and NO synthesis were mimicked by Y27632 (an inhibitor of the Rho-dependent kinases) and toxin B (an inhibitor of RhoA GTPase activity), while they were reverted by mevalonic acid, the product of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. Furthermore, crocidolite, similarly to mevastatin, inhibited the synthesis of cholesterol and ubiquinone and the prenylation of RhoA: these effects were prevented in the presence of mevalonic acid. This suggests that crocidolite fibers might inhibit the synthesis of isoprenoid molecules at the level of the HMGCoA reductase reaction or of an upstream step, thus impairing the prenylation and subsequent activation of RhoA. Akt can stimulate NO synthesis via a double mechanism: it can activate the inducible NO synthase via the NF-kappaB pathway and the endothelial NO synthase via a direct phosphorylation. Our results suggest that crocidolite increases the NO levels in mesothelioma cells by modulating both NO synthase isoforms.

  14. Protein kinase A mediates inhibition of the thrombin-induced platelet shape change by nitric oxide.

    PubMed

    Jensen, Baard Olav; Selheim, Frode; Døskeland, Stein Ove; Gear, Adrian R L; Holmsen, Holm

    2004-11-01

    The thrombin-induced platelet shape change was blocked by nitric oxide (NO), as revealed by scanning electron microscopy, light transmission, and resistive-particle volume determination. The inhibitory effect of NO was accompanied by an increase in levels of both cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) and phosphorylation of the vasodilator-stimulated phosphoprotein (VASP). However, the inhibition of the shape change was only mimicked by cAMP analogs (Sp-5,6-DClcBIMPS, 8-AHA-cAMP, and 8-CPT-cAMP) and not by cGMP analogs (8-Br-PET-cGMP, 8-Br-cGMP, and 8-pCPT-cGMP). The effect of NO on the thrombin-induced shape change was prevented by the protein kinase A (PKA) antagonists Rp-8-Br-cAMPS and Rp-cAMPS. The protein kinase G (PKG) antagonist Rp-8-CPT-cGMPS strongly inhibited PKG-mediated 46-kDa VASP Ser239 phosphorylation, but did not inhibit the thrombin-induced shape change or the PKA-mediated VASP Ser157 phosphorylation. Whereas an inhibitor of cyclic nucleotide phosphodiesterase (PDE) 3A (milrinone) mimicked the effect of NO, inhibitors of PDE2 (erythro-9-(2-hydroxy-3-nonyl)adenine) and PDE5 (dipyridamole) were poorly effective. We concluded that (1) NO was a potent and reversible inhibitor of the platelet shape change, (2) the shape change was reversible, (3) the inhibitory effect of NO was mediated through activation of PKA, (4) the onset of the NO effect coincided with VASP Ser157 phosphorylation, and (5) removal of NO and platelet shape change coincided with VASP Ser157 dephosphorylation. These findings are compatible with elevation of cGMP by NO in a compartment close to PDE3A, PKA, and VASP, leading to a local increase of cAMP able to block thrombin-induced shape change.

  15. A large blood pressure-raising effect of nitric oxide synthase inhibition in humans

    NASA Technical Reports Server (NTRS)

    Sander, M.; Chavoshan, B.; Victor, R. G.; Blomqvist, C. G. (Principal Investigator)

    1999-01-01

    In experimental animals, systemic administration of nitric oxide synthase (NOS) inhibitors causes large increases in blood pressure that are in part sympathetically mediated. The aim of this study was to determine the extent to which these conclusions can be extrapolated to humans. In healthy normotensive humans, we measured blood pressure in response to two NOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), the latter of which recently became available for use in humans. The major new findings are 3-fold. First, L-NAME produced robust increases in blood pressure that were more than 2 times larger than those previously reported in humans with L-NMMA and approximated those seen in experimental animals. L-NAME (4 mg/kg) raised mean arterial pressure by 24+/-2 mm Hg (n=27, P<0.001), whereas in subjects who received both inhibitors, a 12-fold higher dose of L-NMMA (50 mg/kg) raised mean arterial pressure by 15+/-2 mm Hg (n=4, P<0.05 vs L-NAME). Second, the L-NAME-induced increases in blood pressure were caused specifically by NOS inhibition because they were reversed by L-arginine (200 mg/kg, n=12) but not D-arginine (200 mg/kg, n=6) and because NG-nitro-D-arginine methyl ester (4 mg/kg, n=5) had no effect on blood pressure. Third, in humans, there is an important sympathetic component to the blood pressure-raising effect of NOS inhibition. alpha-Adrenergic blockade with phentolamine (0.2 mg/kg, n=9) attenuated the L-NAME-induced increase in blood pressure by 40% (P<0.05). From these data, we conclude that pharmacological inhibition of NOS causes large increases in blood pressure that are in part sympathetically mediated in humans as well as experimental animals.

  16. Isorhamnetin attenuates liver fibrosis by inhibiting TGF-β/Smad signaling and relieving oxidative stress.

    PubMed

    Yang, Ji Hye; Kim, Sang Chan; Kim, Kyu Min; Jang, Chang Ho; Cho, Sam Seok; Kim, Seung Jung; Ku, Sae Kwang; Cho, Il Je; Ki, Sung Hwan

    2016-07-15

    Hepatic fibrosis is considered integral to the progression of chronic liver diseases, leading to the development of cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. We investigated the ability of isorhamnetin, the 3'-O-methylated metabolite of quercetin, to protect against hepatic fibrosis in vitro and in vivo. Isorhamnetin inhibited transforming growth factor (TGF)-β1-induced expression of α-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and collagen in primary murine HSCs and LX-2 cells. The TGF-β1- or Smad-induced luciferase reporter activity of Smad binding elements was significantly decreased by isorhamnetin with a concomitant decrease in Smad2/3 phosphorylation. Isorhamnetin increased the nuclear translocation of Nrf2 in HSCs and increased antioxidant response element reporter gene activity. Furthermore, isorhamnetin blocked TGF-β1-induced reactive oxygen species production. The specific role of Nrf2 in isorhamnetin-mediated suppression of PAI-1 and phosphorylated Smad3 was verified using a siRNA against Nrf2. To examine the anti-fibrotic effect of isorhamnetin in vivo, liver fibrosis was induced by CCl4 in mice. Isorhamnetin significantly prevented CCl4-induced increases in serum alanine transaminase and aspartate transaminase levels, and caused histopathological changes characterized by decreases in hepatic degeneration, inflammatory cell infiltration, and collagen accumulation. Moreover, isorhamnetin markedly decreased the expression of phosphorylated Smad3, TGF-β1, α-SMA, and PAI-1. Isorhamnetin attenuated the CCl4-induced increase in the number of 4-hydroxynonenal and nitrotyrosine-positive cells, and prevented glutathione depletion. We propose that isorhamnetin inhibits the TGF-β/Smad signaling pathway and relieves oxidative stress, thus inhibiting HSC activation and preventing liver fibrosis.

  17. Advanced oxidation protein products inhibit differentiation and activate inflammation in 3T3-L1 preadipocytes.

    PubMed

    Zhou, Qiu Gen; Peng, Xin; Hu, Li Li; Xie, Di; Zhou, Min; Hou, Fan Fan

    2010-10-01

    Accumulation of advanced oxidation protein products (AOPPs) is prevalent in metabolic syndromes, a condition with impaired preadipocytes differentiation. In the present study, we tested the hypothesis that AOPPs disturb preadipocyte differentiation. Exposure of 3T3-L1 preadipocytes to increased levels of AOPPs inhibited accumulation of intracellular triglyceride and decreased the expression of the essential markers of matured adipocytes, such as adipocyte fatty-acid-binding protein (aP2), CAAT/enhancer-binding protein (C/EBP)-alpha, and peroxisome proliferator-activated receptor (PPAR)-gamma, in response to standard adipogenic induction. Inhibitory effects of AOPPs on preadipocytes differentiation was time sensitive, which occurred at the early stage of differentiation. In the presence of AOPPs, induction of preadipocytes differentiation resulted in upregulated expression of C/EBP homologous protein (CHOP) and CUG-Triplet repeat-binding protein (CUGBP), two important inhibitors of preadipocytes differentiation. In addition, treatment with AOPPs increased abundance of C/EBP-beta-liver enriched inhibitory protein (C/EBP-beta-LIP), a truncated C/EBP-beta isoform without adipogenic activity. Moreover, AOPPs-treated preadipocytes expressed a macrophage marker F4/80 and overexpressed tumor necrosis factor-alpha and interleukin-6 via nuclear factor-kappaB (NF-kappaB)-dependent pathway. However, blocking inflammation with NF-kappaB inhibitor failed to improve AOPPs-induced inhibition of preadipocytes differentiation. These data suggest that accumulation of AOPPs may inhibit differentiation of preadipocytes and activate inflammation in these cells. This information might have implication for understanding the impairment of preadipocytes differentiation and fat inflammation seen in metabolic syndrome.

  18. Inhibition of carbon monoxide on methanol oxidation over γ-alumina supported Ag, Pd and Ag Pd catalysts

    NASA Astrophysics Data System (ADS)

    Wang, Jin-an; Aguilar-Ríos, G.; Wang, Ren

    1999-05-01

    The activities of CH 3OH and CO oxidative reactions over the γ-alumina supported Ag, Pd and Ag-Pd catalysts were measured with the MR-GC method. The CO-temperature-programmed desorption (CO-TPD) and in situ IR techniques were used to characterize the CO adsorption behavior on the surface of the catalysts. The oxidative activity for CO to CO 2 increased in the following sequence: 5% Ag/γ-Al 2O 3<0.1% Pd/γ-Al 2O 3<5% Ag-0.1% Pd/γ-Al 2O 3. An inhibition action of CO to CH 3OH oxidation, that is dependent of the active components of the catalysts, was observed when CO was present in the methanol-fed stream. The results of IR and CO-TPD showed that the poor oxidative activity of CO over Ag catalyst was due to its low adsorption capacity on this catalyst. The very strong adsorption ability of CO on the Pd catalyst was responsible for the strong inhibition of CO to CH 3OH oxidation activity. The plausible mechanisms of CO strong inhibition behavior on methanol oxidation over the different catalysts are discussed in detail from the viewpoints of both electronic and geometric effects.

  19. Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress.

    PubMed

    Zheng, Jing; Inoguchi, Toyoshi; Sasaki, Shuji; Maeda, Yasutaka; McCarty, Mark F; Fujii, Masakazu; Ikeda, Noriko; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

    2013-01-15

    We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.

  20. Zinc oxide nanoparticles cause inhibition of microbial denitrification by affecting transcriptional regulation and enzyme activity.

    PubMed

    Zheng, Xiong; Su, Yinglong; Chen, Yinguang; Wan, Rui; Liu, Kun; Li, Mu; Yin, Daqiang

    2014-12-02

    Over the past few decades, human activities have accelerated the rates and extents of water eutrophication and global warming through increasing delivery of biologically available nitrogen such as nitrate and large emissions of anthropogenic greenhouse gases. In particular, nitrous oxide (N2O) is one of the most important greenhouse gases, because it has a 300-fold higher global warming potential than carbon dioxide. Microbial denitrification is a major pathway responsible for nitrate removal, and also a dominant source of N2O emissions from terrestrial or aquatic environments. However, whether the release of zinc oxide nanoparticles (ZnO NPs) into the environment affects microbial denitrification is largely unknown. Here we show that the presence of ZnO NPs lead to great increases in nitrate delivery (9.8-fold higher) and N2O emissions (350- and 174-fold higher in the gas and liquid phases, respectively). Our data further reveal that ZnO NPs significantly change the transcriptional regulations of glycolysis and polyhydroxybutyrate synthesis, which causes the decrease in reducing powers available for the reduction of nitrate and N2O. Moreover, ZnO NPs substantially inhibit the gene expressions and catalytic activities of key denitrifying enzymes. These negative effects of ZnO NPs on microbial denitrification finally cause lower nitrate removal and higher N2O emissions, which is likely to exacerbate water eutrophication and global warming.

  1. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice.

    PubMed

    Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng

    2015-12-01

    Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD.

  2. Experimental inhibition of nitric oxide increases Plasmodium relictum (lineage SGS1) parasitaemia.

    PubMed

    Bichet, Coraline; Cornet, Stéphane; Larcombe, Stephen; Sorci, Gabriele

    2012-12-01

    Malaria is a widespread vector-borne disease infecting a wide range of terrestrial vertebrates including reptiles, birds and mammals. In addition to being one of the most deadly infectious diseases for humans, malaria is a threat to wildlife. The host immune system represents the main defence against malaria parasites. Identifying the immune effectors involved in malaria resistance has therefore become a major focus of research. However, this has mostly involved humans and animal models (rodents) and how the immune system regulates malaria progression in non-model organisms has been largely ignored. The aim of the present study was to investigate the role of nitric oxide (NO) as an immune effector contributing to the control of the acute phase of infection with the avian malaria agent Plasmodium relictum. We used experimental infections of domestic canaries in conjunction with the inhibition of the enzyme inducible nitric oxide synthase (iNOS) to assess the protective function of NO during the infection, and the physiological costs paid by the host in the absence of an effective NO response. Our results show that birds treated with the iNOS inhibitor suffered from a higher parasitaemia, but did not pay a higher cost of infection (anaemia). While these findings confirm that NO contributes to the resistance to avian malaria during the acute phase of the infection, they also suggest that parasitaemia and costs of infection can be decoupled.

  3. Selective inhibition of nitrite oxidation by chlorate dosing in aerobic granules.

    PubMed

    Xu, Guangjing; Xu, Xiaochen; Yang, Fenglin; Liu, Sitong

    2011-01-15

    Partial nitrification was successfully achieved with addition of 5mM KClO(3) in the aerobic granules system. Batch tests demonstrated that KClO(3) selectively inhibited nitrite-oxidizing bacteria (NOB) but not ammonia-oxidizing bacteria (AOB). During stable partial nitrification, the influent pH was kept at 7.8-8.2, while the DO and temperature were not controlled in the SBR. When the NH(4)-N and COD levels were kept at 100mg/l and 400mg/l in the influent, the NH(4)-N and COD removal efficiencies reached 98.93% and 78.65%, respectively. The NO(2)-N accounted for 92.95% of the NO(χ)-N (NO(2)-N+NO(3)-N) in the effluent. Furthermore, about 90% of the chlorate was reduced to nontoxic chloride, thus it would not cause environmental problem. SEM showed that the main composition of the aerobic granules was bacilli and coccus bacteria. FISH analysis revealed that AOB became the dominant nitrifying bacteria, whereas NOB were detected only in low abundance. Chlorate could be used to control the development and maintenance of aerobic granules sludge for partial nitrification.

  4. Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

    PubMed

    Lee, Bonggi; Kwon, Misung; Choi, Jae Sue; Jeong, Hyoung Oh; Chung, Hae Young; Kim, Hyeung-Rak

    2015-12-01

    Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes.

  5. Free radical reaction characteristics of coal low-temperature oxidation and its inhibition method.

    PubMed

    Li, Zenghua; Kong, Biao; Wei, Aizhu; Yang, Yongliang; Zhou, Yinbo; Zhang, Lanzhun

    2016-12-01

    Study on the mechanism of coal spontaneous combustion is significant for controlling fire disasters due to coal spontaneous combustion. The free radical reactions can explain the chemical process of coal at low-temperature oxidation. Electron spin resonance (ESR) spectroscopy was used to measure the change rules of the different sorts and different granularity of coal directly; ESR spectroscopy chart of free radicals following the changes of temperatures was compared by the coal samples applying air and blowing nitrogen, original coal samples, dry coal samples, and demineralized coal samples. The fragmentation process was the key factor of producing and initiating free radical reactions. Oxygen, moisture, and mineral accelerated the free radical reactions. Combination of the free radical reaction mechanism, the mechanical fragmentation leaded to the elevated CO concentration, fracturing of coal pillar was more prone to spontaneous combustion, and spontaneous combustion in goaf accounted for a large proportion of the fire in the mine were explained. The method of added diphenylamine can inhibit the self-oxidation of coal effectively, the action mechanism of diphenylamine was analyzed by free radical chain reaction, and this research can offer new method for the development of new flame retardant.

  6. CLIC1 Inhibition Attenuates Vascular Inflammation, Oxidative Stress, and Endothelial Injury

    PubMed Central

    Hu, Xiao; Wang, Cui; Lu, Dezhao; Gong, Chenxue; Yang, Jinhuan; Zong, Lei

    2016-01-01

    Endothelial dysfunction, which includes endothelial oxidative damage and vascular inflammation, is a key initiating step in the pathogenesis of atherosclerosis (AS) and an independent risk factor for this disorder. Intracellular chloride channel 1 (CLIC1), a novel metamorphic protein, acts as a sensor of cell oxidation and is involved in inflammation. In this study, we hypothesize that CLIC1 plays an important role in AS. Apolipoprotein E-deficient mice were supplied with a normal diet or a high-fat and high-cholesterol diet for 8 weeks. Overexpressed CLIC1 was associated with the accelerated atherosclerotic plaque development, amplified oxidative stress, and in vivo release of inflammatory cytokines. We subsequently examined the underlying molecular mechanisms through in vitro experiments. Treatment of cultured human umbilical vein endothelial cells (HUVECs) with H2O2 induced endothelial oxidative damage and enhanced CLIC1 expression. Suppressing CLIC1 expression through gene knocked-out (CLIC1−/−) or using the specific inhibitor indanyloxyacetic acid-94 (IAA94) reduced ROS production, increased SOD enzyme activity, and significantly decreased MDA level. CLIC1−/− HUVECs exhibited significantly reduced expression of TNF-α and IL-1β as well as ICAM-1 and VCAM-1 at the protein levels. In addition, H2O2 promoted CLIC1 translocation to the cell membrane and insertion into lipid membranes, whereas IAA94 inhibited CLIC1 membrane translocation induced by H2O2. By contrast, the majority of CLIC1 did not aggregate on the cell membrane in normal HUVECs, and this finding is consistent with the changes in cytoplasmic chloride ion concentration. This study demonstrates for the first time that CLIC1 is overexpressed during AS development both in vitro and in vivo and can regulate the accumulation of inflammatory cytokines and production of oxidative stress. Our results also highlight that deregulation of endothelial functions may be associated with the membrane

  7. SERPINA3K Prevents Oxidative Stress Induced Necrotic Cell Death by Inhibiting Calcium Overload

    PubMed Central

    Zhang, Bin; Ma, Jian-xing

    2008-01-01

    Background SERPINA3K, an extracellular serine proteinase inhibitor (serpin), has been shown to have decreased levels in the retinas of diabetic rats, which may contribute to diabetic retinopathy. The function of SERPINA3K in the retina has not been investigated. Methodology/Principal Findings The present study identified a novel function of SERPINA3K, i.e. it protects retinal cells against oxidative stress-induced cell death including retinal neuronal cells and Müller cells. Flow-cytometry showed that the protective effect of SERPINA3K on Müller cells is via reducing oxidation-induced necrosis. Measurements of intracellular calcium concentration showed that SERPINA3K prevented the intracellular calcium overload induced by H2O2. A similar protective effect was observed using a calcium chelator (BAPTA/AM). Further, SERPINA3K inhibited the phosphorylation of phospholipase C (PLC)-gamma1 induced by H2O2. Likewise, a specific PLC inhibitor showed similar protective effects on Müller cells exposed to H2O2. Furthermore, the protective effect of SERPINA3K was attenuated by a specific PLC activator (m-3M3FBS). Finally, in a binding assay, SERPINA3K displayed saturable and specific binding on Müller cells. Conclusion/Significance These results for the first time demonstrate that SERPINA3K is an endogenous serpin which protects cells from oxidative stress-induced cells death, and its protective effect is via blocking the calcium overload through the PLC pathway. The decreased retinal levels of SERPINA3K may represent a new pathogenic mechanism for the retinal Müller cell dysfunction and neuron loss in diabetes. PMID:19115003

  8. Fatty acid synthase inhibits the O-GlcNAcase during oxidative stress.

    PubMed

    Groves, Jennifer A; Maduka, Austin O; O'Meally, Robert N; Cole, Robert N; Zachara, Natasha E

    2017-02-23

    The dynamic post-translational modification O-linked-β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins. Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins and this increase is thought to promote cell survival. The mechanisms by which the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA), the enzymes that add and remove O-GlcNAc respectively, are regulated during oxidative stress to alter O-GlcNAcylation are not fully characterized. Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells, but has little impact on the activity of OGT. In contrast, the expression and activity of OGA are enhanced. We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc. To identify potential protein partners, we utilized BioID proximity biotinylation in combination with Stable Isotope Labeling of Amino Acids in Cell culture (SILAC). This analysis revealed 90 OGA-interacting partners, many of which exhibited increased binding to OGA upon stress. The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70 kDa protein, and OGT were confirmed by co-immunoprecipitation. The pool of OGA bound to FAS demonstrated a substantial (≈85%) reduction in specific activity, suggesting that FAS inhibits OGA. Consistent with this observation, FAS overexpression augmented stress-induced O-GlcNAcylation. While the mechanism by which FAS sequesters OGA remains unknown, these data suggest that FAS fine-tunes the cell's response to stress and injury by remodeling cellular O-GlcNAcylation.

  9. Nitric oxide/cyclic guanosine monophosphate signaling in the central complex of the grasshopper brain inhibits singing behavior.

    PubMed

    Wenzel, Beate; Kunst, Michael; Günther, Cornelia; Ganter, Geoffrey K; Lakes-Harlan, Reinhard; Elsner, Norbert; Heinrich, Ralf

    2005-07-25

    Grasshopper sound production, in the context of mate finding, courtship, and rivalry, is controlled by the central body complex in the protocerebrum. Stimulation of muscarinic acetylcholine receptors in the central complex has been demonstrated to stimulate specific singing in various grasshoppers including the species Chorthippus biguttulus. Sound production elicited by stimulation of muscarinic acetylcholine receptors in the central complex is inhibited by co-applications of various drugs activating the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway. The nitric oxide-donor sodium nitroprusside caused a reversible suppression of muscarine-stimulated sound production that could be blocked by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ), which prevents the formation of cGMP by specifically inhibiting soluble guanylyl cyclase. Furthermore, injections of both the membrane-permeable cGMP analog 8-Br-cGMP and the specific inhibitor of the cGMP-degrading phosphodiesterase Zaprinast reversibly inhibited singing. To identify putative sources of nitric oxide, brains of Ch. biguttulus were subjected to both nitric oxide synthase immunocytochemistry and NADPH-diaphorase staining. Among other areas known to express nitric oxide synthase, both procedures consistently labeled peripheral layers in the upper division of the central body complex, suggesting that neurons supplying this neuropil contain nitric oxide synthase and may generate nitric oxide upon activation. Exposure of dissected brains to nitric oxide and 3-(5'hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) induced cGMP-associated immunoreactivity in both the upper and lower division. Therefore, both the morphological and pharmacological data presented in this study strongly suggest a contribution of the nitric oxide/cGMP signaling pathway to the central control of grasshopper sound production.

  10. The clinical research for Ganoderan's effect on preventing and treating cerebral arteriosclerosis through inhibiting NADPH oxidizing enzyme expression.

    PubMed

    Feng, Zhang Li; Fang, Teng Jun; Qian, Yuan Xue; Rong, Wang Huan

    2014-07-01

    A lot of researches have verified that produced excessive reactive oxygen is one of the hazard factors causing atherosclerosis. NADPH oxidase is the main protease of vascular cell's producing reactive oxygen, the expression of its relevant subunits is closely correlated with the occurring and development process of atherosclerosis. Oxidizing reaction could damage organism tissue cells, ganoderan has very significant effect on the anti-oxidizing function of cell. The pharmaceutical research of ganoderan has significant meaning in curing diabetes mellitus, preventing and controlling arteriosclerosis. This paper is mainly to discuss the effect of anoderan's inhibiting NADPH oxidizing enzyme expression on preventing and treating cerebral arteriosclerosis and its action mechanism.

  11. Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and anticancer drug effectiveness

    PubMed Central

    McAdam, Elizabeth; Brem, Reto; Karran, Peter

    2016-01-01

    The relationship between sun exposure and non-melanoma skin cancer risk is well established. Solar ultraviolet radiation (UV; wavelengths 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 mn) component of solar UV radiation increases skin cancer risk is not understood. We demonstrate here that the contribution of UVA to the effects of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the cells’ susceptibility to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Statement of implication: Since NER is both a defence against cancer a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative-stress has implications for both cancer risk and for the effectiveness of anticancer therapy. PMID:27106867

  12. Strategies for dynamic soft-landing in capacitive microelectromechanical switches

    NASA Astrophysics Data System (ADS)

    Jain, Ankit; Nair, Pradeep R.; Alam, Muhammad A.

    2011-06-01

    Electromechanical dielectric degradation associated with the hard landing of movable electrode is a technology-inhibiting reliability concern for capacitive RF-MEMS switches. In this letter, we propose two schemes for dynamic soft-landing that obviate the need for external feedback circuitry. Instead, the proposed resistive and capacitive braking schemes can reduce impact velocity significantly without compromising other performance characteristics like pull-in voltage and pull-in time. Resistive braking is achieved by inserting a resistance in series with the voltage source whereas capacitive braking requires patterning of the electrode or the dielectric. Our results have important implications to the design and optimization of reliability aware electrostatically actuated MEMS switches.

  13. Electrochemically reduced graphene and iridium oxide nanoparticles for inhibition-based angiotensin-converting enzyme inhibitor detection.

    PubMed

    Kurbanoglu, Sevinc; Rivas, Lourdes; Ozkan, Sibel A; Merkoçi, Arben

    2017-02-15

    In this work, a novel biosensor based on electrochemically reduced graphene oxide and iridium oxide nanoparticles for the detection of angiotensin-converting enzyme inhibitor drug, captopril, is presented. For the preparation of the biosensor, tyrosinase is immobilized onto screen printed electrode by using 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-Hydroxysuccinimide coupling reagents, in electrochemically reduced graphene oxide and iridium oxide nanoparticles matrix. Biosensor response is characterized towards catechol, in terms of graphene oxide concentration, number of cycles to reduce graphene oxide, volume of iridium oxide nanoparticles and tyrosinase solution. The designed biosensor is used to inhibit tyrosinase activity by Captopril, which is generally used to treat congestive heart failure. It is an angiotensin-converting enzyme inhibitor that operates via chelating copper at the active site of tyrosinase and thioquinone formation. The captopril detections using both inhibition ways are very sensitive with low limits of detection: 0.019µM and 0.008µM for chelating copper at the active site of tyrosinase and thioquinone formation, respectively. The proposed methods have been successfully applied in captopril determination in spiked human serum and pharmaceutical dosage forms with acceptable recovery values.

  14. Oxidative Damage Control in a Human (Mini-) Organ: Nrf2 Activation Protects against Oxidative Stress-Induced Hair Growth Inhibition.

    PubMed

    Haslam, Iain S; Jadkauskaite, Laura; Szabó, Imre Lőrinc; Staege, Selma; Hesebeck-Brinckmann, Jasper; Jenkins, Gail; Bhogal, Ranjit K; Lim, Fei-Ling; Farjo, Nilofer; Farjo, Bessam; Bíró, Tamás; Schäfer, Matthias; Paus, Ralf

    2017-02-01

    The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the "master regulator" of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than only in isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ: scalp hair follicles. Microarray and qRT-PCR analysis of human hair follicles after Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, reactive oxygen species clearance, the pentose phosphate pathway, and glutathione homeostasis. Nrf2 knockdown (small interfering RNA) in cultured human hair follicles confirmed the regulation of key Nrf2 target genes (i.e., heme oxygenase-1, NAD(P)H dehydrogenase, quinone 1, glutathione reductase, glutamate-cysteine ligase catalytic subunit, ABCC1, peroxiredoxin 1). Importantly, Nrf2 activation significantly reduced reactive oxygen species levels and associated lipid peroxidation. Nrf2 preactivation reduced premature catagen and hair growth inhibition induced by oxidative stress (H2O2 or menadione), significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the reactive oxygen species-induced reduction in hair matrix proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e., scalp hair follicles) against redox insult.

  15. 1,5-Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid-β(1-40) Fibrillization.

    PubMed

    Tsutsui, Ayumi; Zako, Tamotsu; Bu, Tong; Yamaguchi, Yoshiki; Maeda, Mizuo; Tanaka, Katsunori

    2016-10-01

    Biologically relevant 1,5-diazacyclooctanes derived from polyamines and acrolein, inhibit Aβ40 peptide fibrillization and significantly suppress cell cytotoxicity. Formal [4+4] cycloaddition reaction of imines is thus involved in modulating oxidative stress processes associated with neural diseases.

  16. Zinc oxide tetrapods inhibit herpes simplex virus infection of cultured corneas

    PubMed Central

    Duggal, Neil; Jaishankar, Dinesh; Yadavalli, Tejabhiram; Hadigal, Satvik; Mishra, Yogendra Kumar; Adelung, Rainer

    2017-01-01

    Purpose Infection of the human cornea by herpes simplex virus type-1 (HSV-1) can cause significant vision loss. The purpose of this study was to develop an ex vivo model to visualize viral growth and spread in the cornea. The model was also used to analyze cytokine production and study the antiviral effects of zinc oxide tetrapods. Methods A β-galactosidase-expressing recombinant virus, HSV-1(KOS)tk12, was used to demonstrate the ability of the virus to enter and develop blue plaques on human corneal epithelial (HCE) cells and corneal tissues. Freshly obtained porcine corneas were cultured and then scratched before infection with HSV-1(KOS)tk12. The blue plaques on the corneas were imaged using a stereomicroscope. Western blot analysis for HSV-1 proteins was performed to verify HSV-1 infection of the cornea. Using the ex vivo model, zinc oxide tetrapods were tested for their anti-HSV-1 potential, and a cytokine profile was developed to assess the effects of the treatment. Results Cultured corneas and the use of β-galactosidase-expressing HSV-1(KOS)tk12 virus can provide an attractive ex vivo model to visualize and study HSV-1 entry and spread of the infection in tissues. We found that unlike cultured HCE cells, which demonstrated nearly 100% infectivity, HSV-1 infection of the cultured cornea was more restrictive and took longer to develop. We also found that the zinc oxide tetrapod–shaped nano- and microstructures inhibited HSV infection of the cultured cells, as well as the cultured corneas. The cytokine profile of the infected samples was consistent with previous studies of HSV-1 corneal infection. Conclusions The ability to visualize HSV-1 growth and spread in corneal tissues can provide new details about HSV-1 infection of the cornea and the efficacy of new cornea-specific antiviral drug candidates. The ex vivo model also demonstrates antiviral effects of zinc oxide tetrapods and adequately portrays the drug delivery issues that cornea-specific treatments

  17. AMP‐activated protein kinase inhibits Kv1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation

    PubMed Central

    Moral‐Sanz, Javier; Mahmoud, Amira D.; Ross, Fiona A.; Eldstrom, Jodene; Fedida, David; Hardie, D. Grahame

    2016-01-01

    Key points Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (Kv) in pulmonary arterial smooth muscle by hypoxia, although the precise molecular mechanisms have been unclear.AMP‐activated protein kinase (AMPK) has been proposed to couple inhibition of mitochondrial metabolism by hypoxia to acute hypoxic pulmonary vasoconstriction and progression of pulmonary hypertension.Inhibition of complex I of the mitochondrial electron transport chain activated AMPK and inhibited Kv1.5 channels in pulmonary arterial myocytes.AMPK activation by 5‐aminoimidazole‐4‐carboxamide riboside, A769662 or C13 attenuated Kv1.5 currents in pulmonary arterial myocytes, and this effect was non‐additive with respect to Kv1.5 inhibition by hypoxia and mitochondrial poisons.Recombinant AMPK phosphorylated recombinant human Kv1.5 channels in cell‐free assays, and inhibited K+ currents when introduced into HEK 293 cells stably expressing Kv1.5.These results suggest that AMPK is the primary mediator of reductions in Kv1.5 channels following inhibition of mitochondrial oxidative phosphorylation during hypoxia and by mitochondrial poisons. Abstract Progression of hypoxic pulmonary hypertension is thought to be due, in part, to suppression of voltage‐gated potassium channels (Kv) in pulmonary arterial smooth muscle cells that is mediated by the inhibition of mitochondrial oxidative phosphorylation. We sought to determine the role in this process of the AMP‐activated protein kinase (AMPK), which is intimately coupled to mitochondrial function due to its activation by LKB1‐dependent phosphorylation in response to increases in the cellular AMP:ATP and/or ADP:ATP ratios. Inhibition of complex I of the mitochondrial electron transport chain using phenformin activated AMPK and inhibited Kv currents in pulmonary arterial myocytes, consistent with previously reported effects of mitochondrial inhibitors. Myocyte

  18. Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition.

    PubMed

    Wang, Qian; Guo, Wenjing; Hao, Baixia; Shi, Xianli; Lu, Yingying; Wong, Connie W M; Ma, Victor W S; Yip, Timothy T C; Au, Joseph S K; Hao, Quan; Cheung, King-Ho; Wu, Wutian; Li, Gui-Rong; Yue, Jianbo

    2016-08-02

    Reactive oxygen species (ROS) have been commonly accepted as inducers of autophagy, and autophagy in turn is activated to relieve oxidative stress. Yet, whether and how oxidative stress, generated in various human pathologies, regulates autophagy remains unknown. Here, we mechanistically studied the role of TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated Ca(2+) influx in oxidative stress-mediated autophagy regulation. On the one hand, we demonstrated that oxidative stress triggered TRPM2-dependent Ca(2+) influx to inhibit the induction of early autophagy, which renders cells more susceptible to death. On the other hand, oxidative stress induced autophagy (and not cell death) in the absence of the TRPM2-mediated Ca(2+) influx. Moreover, in response to oxidative stress, TRPM2-mediated Ca(2+) influx activated CAMK2 (calcium/calmodulin dependent protein kinase II) at levels of both phosphorylation and oxidation, and the activated CAMK2 subsequently phosphorylated BECN1/Beclin 1 on Ser295. Ser295 phosphorylation of BECN1 in turn decreased the association between BECN1 and PIK3C3/VPS34, but induced binding between BECN1 and BCL2. Clinically, acetaminophen (APAP) overdose is the most common cause of acute liver failure worldwide. We demonstrated that APAP overdose also activated ROS-TRPM2-CAMK2-BECN1 signaling to suppress autophagy, thereby causing primary hepatocytes to be more vulnerable to death. Inhibiting the TRPM2-Ca(2+)-CAMK2 cascade significantly mitigated APAP-induced liver injury. In summary, our data clearly demonstrate that oxidative stress activates the TRPM2-Ca(2+)-CAMK2 cascade to phosphorylate BECN1 resulting in autophagy inhibition.

  19. ROS-Mediated Inhibition of S-nitrosoglutathione Reductase Contributes to the Activation of Anti-oxidative Mechanisms

    PubMed Central

    Kovacs, Izabella; Holzmeister, Christian; Wirtz, Markus; Geerlof, Arie; Fröhlich, Thomas; Römling, Gaby; Kuruthukulangarakoola, Gitto T.; Linster, Eric; Hell, Rüdiger; Arnold, Georg J.; Durner, Jörg; Lindermayr, Christian

    2016-01-01

    Nitric oxide (NO) has emerged as a signaling molecule in plants being involved in diverse physiological processes like germination, root growth, stomata closing and response to biotic and abiotic stress. S-nitrosoglutathione (GSNO) as a biological NO donor has a very important function in NO signaling since it can transfer its NO moiety to other proteins (trans-nitrosylation). Such trans-nitrosylation reactions are equilibrium reactions and depend on GSNO level. The breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR). In this way, this enzyme controls S-nitrosothiol levels and regulates NO signaling. Here we report that Arabidopsis thaliana GSNOR activity is reversibly inhibited by H2O2 in vitro and by paraquat-induced oxidative stress in vivo. Light scattering analyses of reduced and oxidized recombinant GSNOR demonstrated that GSNOR proteins form dimers under both reducing and oxidizing conditions. Moreover, mass spectrometric analyses revealed that H2O2-treatment increased the amount of oxidative modifications on Zn2+-coordinating Cys47 and Cys177. Inhibition of GSNOR results in enhanced levels of S-nitrosothiols followed by accumulation of glutathione. Moreover, transcript levels of redox-regulated genes and activities of glutathione-dependent enzymes are increased in gsnor-ko plants, which may contribute to the enhanced resistance against oxidative stress. In sum, our results demonstrate that reactive oxygen species (ROS)-dependent inhibition of GSNOR is playing an important role in activation of anti-oxidative mechanisms to damping oxidative damage and imply a direct crosstalk between ROS- and NO-signaling. PMID:27891135

  20. Bilirubin scavenges chloramines and inhibits myeloperoxidase-induced protein/lipid oxidation in physiologically relevant hyperbilirubinemic serum.

    PubMed

    Boon, A C; Hawkins, C L; Coombes, J S; Wagner, K H; Bulmer, A C

    2015-09-01

    Hypochlorous acid (HOCl), an oxidant produced by myeloperoxidase (MPO), induces protein and lipid oxidation, which is implicated in the pathogenesis of atherosclerosis. Individuals with mildly elevated bilirubin concentrations (i.e., Gilbert syndrome; GS) are protected from atherosclerosis, cardiovascular disease, and related mortality. We aimed to investigate whether exogenous/endogenous unconjugated bilirubin (UCB), at physiological concentrations, can protect proteins/lipids from oxidation induced by reagent and enzymatically generated HOCl. Serum/plasma samples supplemented with exogenous UCB (≤250µM) were assessed for their susceptibility to HOCl and MPO/H2O2/Cl(-) oxidation, by measuring chloramine, protein carbonyl, and malondialdehyde (MDA) formation. Serum/plasma samples from hyperbilirubinemic Gunn rats and humans with GS were also exposed to MPO/H2O2/Cl(-) to: (1) validate in vitro data and (2) determine the relevance of endogenously elevated UCB in preventing protein and lipid oxidation. Exogenous UCB dose-dependently (P<0.05) inhibited HOCl and MPO/H2O2/Cl(-)-induced chloramine formation. Albumin-bound UCB efficiently and specifically (3.9-125µM; P<0.05) scavenged taurine, glycine, and N-α-acetyllysine chloramines. These results were translated into Gunn rat and GS serum/plasma, which showed significantly (P<0.01) reduced chloramine formation after MPO-induced oxidation. Protein carbonyl and MDA formation was also reduced after MPO oxidation in plasma supplemented with UCB (P<0.05; 25 and 50µM, respectively). Significant inhibition of protein and lipid oxidation was demonstrated within the physiological range of UCB, providing a hypothetical link to protection from atherosclerosis in hyperbilirubinemic individuals. These data demonstrate a novel and physiologically relevant mechanism whereby UCB could inhibit protein and lipid modification by quenching chloramines induced by MPO-induced HOCl.

  1. CMOS capacitive biosensors for highly sensitive biosensing applications.

    PubMed

    Chang, An-Yu; Lu, Michael S-C

    2013-01-01

    Magnetic microbeads are widely used in biotechnology and biomedical research for manipulation and detection of cells and biomolecules. Most lab-on-chip systems capable of performing manipulation and detection require external instruments to perform one of the functions, leading to increased size and cost. This work aims at developing an integrated platform to perform these two functions by implementing electromagnetic microcoils and capacitive biosensors on a CMOS (complementary metal oxide semiconductor) chip. Compared to most magnetic-type sensors, our detection method requires no externally applied magnetic fields and the associated fabrication is less complicated. In our experiment, microbeads coated with streptavidin were driven to the sensors located in the center of microcoils with functionalized anti-streptavidin antibody. Detection of a single microbead was successfully demonstrated using a capacitance-to-frequency readout. The average capacitance changes for the experimental and control groups were -5.3 fF and -0.2 fF, respectively.

  2. Unified capacitance modelling of MOSFETs

    NASA Astrophysics Data System (ADS)

    Johannessen, O. G.; Fjeldly, T. A.; Ytterdal, T.

    1994-01-01

    A unified physics based capacitance model for MOSFETs suitable for implementation in circuit simulators is presented. This model is based on the charge conserving, so-called Meyer-like approach proposed by Turchetti et al., and utilizes a unified charge control model to assure a continuous description of the MOSFET capacitances both above and below threshold. The capacitances associated with the model are comparable to those of the well-known BSIM model in the above-threshold regime, but it is more precise in the description of near-threshold and subthreshold behaviour. Moreover, the discontinuities at the transitions between the various regimes of operation are removed. The present modelling scheme was implemented in our circuit simulator AIM-Spice, and simulations of the dynamic behaviour of various demanding benchmark circuits clearly reveal its superiority over simulations using the simple Meyer model.

  3. The Capacitive Magnetic Field Sensor

    NASA Astrophysics Data System (ADS)

    Zyatkov, D. O.; Yurchenko, A. V.; Balashov, V. B.; Yurchenko, V. I.

    2016-01-01

    The results of a study of sensitive element magnetic field sensor are represented in this paper. The sensor is based on the change of the capacitance with an active dielectric (ferrofluid) due to the magnitude of magnetic field. To prepare the ferrofluid magnetic particles are used, which have a followingdispersion equal to 50 < Ø < 56, 45 < Ø < 50, 40 < Ø < 45 and Ø < 40micron of nanocrystalline alloy of brand 5BDSR. The dependence of the sensitivity of the capacitive element from the ferrofluid with different dispersion of magnetic particles is considered. The threshold of sensitivity and sensitivity of a measuring cell with ferrofluid by a magnetic field was determined. The experimental graphs of capacitance change of the magnitude of magnetic field are presented.

  4. Anti-cytochrome P450 IIE1 (anti IIE1) and dimethyl sulfoxide inhibit acetaminophen and dimethylnitrosamine oxidation similarly

    SciTech Connect

    Jaw, S.; Jeffery, E.H. ); Roberts, D.W. )

    1991-03-11

    To evaluate specificity of dimethyl sulfoxide (DMSO), the authors compared anti IIE1 and DMSO inhibition of P450 oxidations. Hepatic microsomes from control and acetone-induced female Swiss-Webster mice were preincubated with polyclonal anti IIE1 or IgG for 20 min at 4C before addition of an NADPH-generating system, DMSO or buffer, and substrate (Ethylmorphine, EM; dimethylnitrosamine, DMN; or acetaminophen, AP; 1 mM final concentration). After 20 min at 37C, the incubations were terminated by adding 20% trichloroacetic acid or methanol. Formaldehyde was determined by the Nash method when using EM or DMN as substrate. AP-glutathione conjugate was determined by HPLC when using AP as substrate. Anti IIE1 and DMSO did not inhibit EM demethylation in control or acetone microsomes. However, DMSO inhibited DMN demethylation by 26% and 64% in control and 30% and 75% in acetone microsomes. Anti IIE1 inhibited DMN demethylation by 44% and 24% in control and acetone microsomes, respectively. DMSO inhibited AP metabolism by 31% and 56% and anti IIE1 inhibited AP metabolism by 33%, in control microsomes. The inhibitions of DMN and AP metabolism by anti IIE1 and DMSO were only additive at submaximal inhibitor concentrations and confirm that DMSO specifically inhibits IIE1 activity.

  5. Realization of Negative Capacitance with Topological Insulator Based MOS Capacitor

    NASA Astrophysics Data System (ADS)

    Yuan, Hui; Zhang, Kai; Zhu, Hao; Li, Haitao; Ioannou, Dimitris; Baumgart, Helmut; Richter, Curt; Li, Qiliang; ECE, George Mason University Team; Semiconductor and Dimensional Metrology Division of NIST Team; ECE, Old Dominion University Team

    2013-03-01

    Negative capacitance is one of way to achieve steep subthreshold slope exceeding its thermal limit in metal-oxide-semiconductor field effect transistor (MOSFET). The common materials under study for negative capacitance are ferroelectric thin films. However, the integration of regular ferroelectric materials (e.g., PZT) into semiconductor based devices is usually difficult due to the high temperature required for crystallization and precise control of oxygen percentage in ferroelectric materials. In this work, we found that negative capacitance can be achieved by introducing a topological insulator interlayer into a conventional MOS capacitor. Three-dimensional topological insulators inherently contain a insulator/semiconductor bulk and a gapless conducting surface. When an electric field is added to topological insulator interlayer, imbalanced charge carriers (electrons and holes) would be generated and then accumulate on either surface of the film, resulting in a temporary residual polarization. As a result, a ferroelectric-like hysteresis and negative capacitance are achieved. We believe this approach will be very attractive to achieve steep subthreshold using negative capacitance. Supported by NSF Career grant 0846649.

  6. Normalization of Supine Blood Pressure After Nitric Oxide Synthase Inhibition in Persons With Tetraplegia

    PubMed Central

    Wecht, Jill M; Weir, Joseph P; Krothe, AnnMarie H; Spungen, Ann M; Bauman, William A

    2007-01-01

    Background/Objective: Orthostatic hypotension is a well-defined clinical consequence of spinal cord injury (SCI), particularly in those with tetraplegia. The etiology of orthostatic hypotension is thought to be loss of sympathetic vasomotor control, although other factors may play a role. There is evidence of up-regulation of nitric oxide synthase (NOS) activity after hind-limb suspension in rats, a condition of antigravity that may have similar vascular effects as shown in persons with tetraplegia caused by paralysis. The study objective was to determine the effect of a NOS inhibitor (nitro-L-arginine methyl ester [L-NAME]) on supine mean arterial pressure in persons with chronic tetraplegia compared with non-SCI controls. Methods: Fourteen individuals participated (7 with tetraplegia and 7 controls). Subjects visited the laboratory twice for placebo on day 1 and L-NAME (1 mg/kg) on day 2; both were infused intravenously over 60 minutes. Blood pressure was monitored for 3 hours after infusion at the brachial artery using a standard manual cuff. Results: Mean arterial pressure (MAP) was lower at baseline (P < 0.05) and after placebo administration (P < 0.0001) in the tetraplegia group compared with the control group. L-NAME increased MAP in both groups; however, the relative increase was greater in the tetraplegia group compared with the control group, such that group differences for MAP were eliminated. Supine MAP was normalized with L-NAME, and there was an increased sensitivity to NOS inhibition in the group with tetraplegia. Conclusions: These findings indicate that blood pressure dysregulation in persons with tetraplegia may reflect increased vascular NO and suggest a novel treatment of hypotension using NOS inhibition in this population. PMID:17385265

  7. Packed Red Blood Cells Are an Abundant and Proximate Potential Source of Nitric Oxide Synthase Inhibition

    PubMed Central

    Zwemer, Charles F.; Davenport, Robertson D.; Gomez-Espina, Juan; Blanco-Gonzalez, Elisa; Whitesall, Steven E.; D'Alecy, Louis G.

    2015-01-01

    Objective We determined, for packed red blood cells (PRBC) and fresh frozen plasma, the maximum content, and ability to release the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethylarginine (LNMMA). Background ADMA and LNMMA are near equipotent NOS inhibitors forming blood’s total NOS inhibitory content. The balance between removal from, and addition to plasma determines their free concentrations. Removal from plasma is by well-characterized specific hydrolases while formation is restricted to posttranslational protein methylation. When released into plasma they can readily enter endothelial cells and inhibit NOS. Fresh rat and human whole blood contain substantial protein incorporated ADMA however; the maximum content of ADMA and LNMMA in PRBC and fresh frozen plasma has not been determined. Methods We measured total (free and protein incorporated) ADMA and LNMMA content in PRBCs and fresh frozen plasma, as well as their incubation induced release, using HPLC with fluorescence detection. We tested the hypothesis that PRBC and fresh frozen plasma contain substantial inhibitory methylarginines that can be released chemically by complete in vitro acid hydrolysis or physiologically at 37°C by enzymatic blood proteolysis. Results In vitro strong-acid-hydrolysis revealed a large PRBC reservoir of ADMA (54.5 ± 9.7 µM) and LNMMA (58.9 ± 28.9 μM) that persisted over 42-d at 6° or -80°C. In vitro 5h incubation at 37°C nearly doubled free ADMA and LNMMNA concentration from PRBCs while no change was detected in fresh frozen plasma. Conclusion The compelling physiological ramifications are that regardless of storage age, 1) PRBCs can rapidly release pathologically relevant quantities of ADMA and LNMMA when incubated and 2) PRBCs have a protein-incorporated inhibitory methylarginines reservoir 100 times that of normal free inhibitory methylarginines in blood and thus could represent a clinically relevant and proximate

  8. Angiotensin II AT1 receptor antagonists inhibit platelet adhesion and aggregation by nitric oxide release.

    PubMed

    Kalinowski, Leszek; Matys, Tomasz; Chabielska, Ewa; Buczko, Włodzimierz; Malinski, Tadeusz

    2002-10-01

    This study investigated the process of nitric oxide (NO) release from platelets after stimulation with different angiotensin II type 1 (AT1)-receptor antagonists and its effect on platelet adhesion and aggregation. Angiotensin II AT1-receptor antagonist-stimulated NO release in platelets was compared with that in human umbilical vein endothelial cells by using a highly sensitive porphyrinic microsensor. In vitro and ex vivo effects of angiotensin II AT1-receptor antagonists on platelet adhesion to collagen and thromboxane A2 analog U46619-induced aggregation were evaluated. Losartan, EXP3174, and valsartan alone caused NO release from platelets and endothelial cells in a dose-dependent manner in the range of 0.01 to 100 micro mol/L, which was attenuated by NO synthase inhibitor N(G)-nitro-L-arginine methyl ester. The angiotensin II AT1-receptor antagonists had more than 70% greater potency in NO release in platelets than in endothelial cells. The degree of inhibition of platelet adhesion (collagen-stimulated) and aggregation (U46619-stimulated) elicited by losartan, EXP3174, and valsartan, either in vitro or ex vivo, closely correlated with the NO levels produced by each of these drugs alone. The inhibiting effects of angiotensin II AT1-receptor antagonists on collagen-stimulated adhesion and U46619-stimulated aggregation of platelets were significantly reduced by pretreatment with N(G)-nitro-L-arginine methyl ester. Neither the AT2 receptor antagonist PD123319, the cyclooxygenase synthase inhibitor indomethacin, nor the selective thromboxane A2/prostaglandin H2 receptor antagonist SQ29,548 had any effect on angiotensin II AT1-receptor antagonist-stimulated NO release in platelets and endothelial cells. The presented studies clearly indicate a crucial role of NO in the arterial antithrombotic effects of angiotensin II AT1-receptor antagonists.

  9. Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production.

    PubMed

    Alfajaro, Mia Madel; Choi, Jong-Soon; Kim, Deok-Song; Seo, Ja-Young; Kim, Ji-Yun; Park, Jun-Gyu; Soliman, Mahmoud; Baek, Yeong-Bin; Cho, Eun-Hyo; Kwon, Joseph; Kwon, Hyung-Jun; Park, Su-Jin; Lee, Woo Song; Kang, Mun-Il; Hosmillo, Myra; Goodfellow, Ian; Cho, Kyoung-Oh

    2017-02-01

    Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection.

  10. Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

    PubMed

    Li, Qin; Bi, Ming Jun; Bi, Wei Kang; Kang, Hai; Yan, Le Jing; Guo, Yun-Liang

    2016-03-01

    Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning.

  11. Inhibition of inducible nitric oxide synthase expression by yuccaol C from Yucca schidigera roezl.

    PubMed

    Marzocco, Stefania; Piacente, Sonia; Pizza, Cosimo; Oleszek, Wieslaw; Stochmal, Anna; Pinto, Aldo; Sorrentino, Raffaella; Autore, Giuseppina

    2004-08-06

    Yucca schidigera extract finds wide commercial application in foods, cosmetics and pharmaceuticals. In a previous paper we have found as the main constituents of yucca bark, yuccaol A, B and C, new and very unusual spiro-derivatives made up of a C15 unit and a stilbenic portion closely related to resveratrol. This study was performed to examine whether yuccaol A, B or C (0.01-100 microM) could affect cytosolic inducible nitric oxide synthase (iNOS) protein expression and nitric oxide (NO) generation in vitro in Escherichia coli lipopolysaccharide (LPS)-activated J774.A1 macrophage cell line. NO production, detected as NO2-, increased significantly in LPS treated J774.A1 cells from 0.05 +/- 0.03 microM to 16.64 +/- 0.58 microM (P < 0.001). Yuccaol C (0.01-100 microM), added to the culture medium 1 h before LPS-stimulation, significantly (P < 0.001) and in a concentration related manner reduced NO release (P < 0.001) and iNOS protein expression (P < 0.05). In contrast, no inhibitory effect either on iNOS protein expression or on NO release was observed when yuccaol C was added after LPS stimulation. In contrast yuccaol A inhibited significantly (P < 0.001) only NO release at the highest concentration tested (100 microM) while yuccaol B did not reduce either NO release or iNOS expression. Yuccaol C was demonstrated to reduce iNOS protein expression via the transcription factor NF-kappaB. These results indicated that the empirical use of Y. schidigera as anti-inflammatory remedy could be addressed not only to the resveratrol content but also to the presence of yuccaol C.

  12. Inhibition of Cathepsin B by E-64 Induces Oxidative Stress and Apoptosis in Filarial Parasite

    PubMed Central

    Wadhawan, Mohit; Singh, Neetu; Rathaur, Sushma

    2014-01-01

    Background Current available antifilarial drug strategies only eliminate the larval stages of filarial parasites. Therefore, there is an urgent need of drugs which are macrofilaricidals. Identification of molecular targets crucial for survival of parasite is a prerequisite for drug designing. Cathepsin B, a cysteine protease family member is known to play crucial role in the normal growth, digestion of nutrients, exsheathment of the helminth parasites. Therefore, we targeted this enzyme in the filarial parasite using its specific inhibitor, E-64. Methods and Findings We have exposed the parasites to E-64 and observed their motility and viability at various time intervals. It caused marked decrease in the motility and viability of the parasites ultimately leading to their death after 8 hours. It is well known that E-64 protects the cell from apoptosis, however, it causes apoptotic effect in carcinoma cell lines. To understand the mechanism of action of E-64 on parasite survival, we have measured levels of different apoptotic markers in the treated parasites. E-64 significantly reduced the level of ced-9 and activity of tyrosine phosphatases, cytochrome c oxidase. It also activated ced-3, homolog of mammalian caspase 3 suggesting initiation of an apoptotic like event in the filarial parasites. Different antioxidant enzymes were also evaluated to further explore the mechanism behind the death of the parasites. There was marked decrease in the level of GSH and activity of Glutathione reductase and glutathione-s-transferase leading to increased generation of reactive oxygen species. This led to the induced oxidation of fatty acids and protein which might alter the mitochondrial membrane permeability. Conclusion This study suggests that inhibition of cathepsin B by E-64 generates oxidative stress followed by mitochondrial mediated apoptotic like event in filarial parasites leading to their death. Hence, suggesting filarial cathepsin B as a potential chemotherapeutic

  13. Pb-inhibited mitotic activity in onion roots involves DNA damage and disruption of oxidative metabolism.

    PubMed

    Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2014-09-01

    Plant responses to abiotic stress significantly affect the development of cells, tissues and organs. However, no studies correlating Pb-induced mitotic inhibition and DNA damage and the alterations in redox homeostasis during root division per se were found in the literature. Therefore, an experiment was conducted to evaluate the impact of Pb on mitotic activity and the associated changes in the oxidative metabolism in onion roots. The cytotoxic effect of Pb on cell division was assessed in the root meristems of Allium cepa (onion). The mitotic index (MI) was calculated and chromosomal abnormalities were sought. Pb-treatment induced a dose-dependent decrease in MI in the onion root tips and caused mitotic abnormalities such as distorted metaphase, fragments, sticky chromosomes, laggards, vagrant chromosomes and bridges. Single Cell Gel Electrophoresis was also performed to evaluate Pb induced genotoxicity. It was accompanied by altered oxidative metabolism in the onion root tips suggesting the interference of Pb with the redox homeostasis during cell division. There was a higher accumulation of malondialdehyde, conjugated dienes and hydrogen peroxide, and a significant increase in the activities of superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases in Pb-treated onion roots, whereas catalases activity exhibited a decreasing pattern upon Pb exposure. The study concludes that Pb-induced cytotoxicity and genotoxicity in the onion roots is mediated through ROS and is also tightly linked to the cell cycle. The exposure to higher concentrations arrested cell cycle leading to cell death, whereas different repair responses are generated at lower concentrations, thereby allowing the cell to complete the cell cycle.

  14. Nitric-oxide inhibits nyctinastic closure through cGMP in Albizia lophantha leaflets.

    PubMed

    Bergareche, Carmen; Moysset, Luisa; Angelo, Alcira Paola; Chellik, Samira; Simón, Esther

    2014-09-01

    Nitric oxide (NO) is a highly reactive radical that acts as a direct or indirect cellular signalling molecule in plant growth, development and environmental responses. Here we studied the contribution of NO to the control of leaflet movements during nyctinastic closure. For this purpose, we tested the effect of NO donors and an NO scavenger, all supplied in light, on Albizia lophantha leaflet closure after transferral to darkness. Exogenous NO, applied as four donors [sodium nitroprusside (SNP), diethylammonium (Z)-1-(N,N-diethylamino) diazen-1-ium-1,2-diolate (DEA-NONOate), S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GS-NO)], inhibited nyctinastic leaflet closure while the application of an NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO)] plus SNP cancelled the effect of the latter. The inclusion of Nω-nitro-l-arginine methyl ester (l-NAME) or sodium tungstate in the incubation media enhanced nyctinastic closure and also resulted in a decrease in the nitrate plus nitrite released by leaflets into the incubation solution. These results support the notion that NO is involved in regulating the nyctinastic closure of A. lophantha leaflets. Cellular perception of NO did not appear to be mediated by calcium. Pharmacological application of inhibitors of soluble guanylate cyclase (sGC) [1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ) and 6-anilino-5,8-quinolinequinone (Ly83583)], phosphodiesterase type 5 (PDE5) (Sildenafil) and the cyclic guanosine monophosphate (cGMP) analogue 8-bromoguanosine-3',5'-cyclomonophosphate sodium salt (8-Br-cGMP) indicated that cGMP was downstream of the NO signalling cascade during nyctinastic closure.

  15. Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose.

    PubMed

    Liu, Weihua; Liu, Peiqinq; Tao, Sha; Deng, Yanhui; Li, Xuejuan; Lan, Tian; Zhang, Xiaoyan; Guo, Fenfen; Huang, Wenge; Chen, Fengying; Huang, Heqing; Zhou, Shu-Feng

    2008-07-15

    Diabetic nephropathy (DN), one of the most serious microvascular complications of diabetes mellitus, is a major cause of end-stage renal disease. Berberine is one of the main constituents of Coptidis rhizoma and Cortex phellodendri. In the present study, we examined effects of berberine (BBR) on renal injury in streptozotocin-induced diabetic rats, and on the changes of aldose reductase (AR) and oxidative stress in cultured rat mesangial cells exposed to high glucose. Fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were detected by using the commercially available kits. Cell proliferation, collagen synthesis, aldose reductase (AR), superoxide anion, superoxide dismutase (SOD), and malondialdehyde (MDA) were detected, respectively, by different methods. In streptozotocin-induced diabetic rats, fasting blood glucose, blood urea nitrogen, creatinine, and urine protein over 24 h were significantly decreased in rats treated with 200 mg/kg berberine for 12 weeks compared with diabetic control rats (P < 0.05). This was accompanied by a reduced AR activity and gene expression at both mRNA and protein levels. In cultured rat mesangial cells exposed to high glucose, incubation of BBR significantly decreased cell proliferation, collagen synthesis and AR activity as well as its mRNA and protein levels compared with control cells (P < 0.05). In vitro, BBR also significantly increased SOD activity and decreased superoxide anion and MDA compared with control cells (P < 0.05). These results suggested that BBR could ameliorate renal dysfunction in DN rats, which may be ascribed to inhibition of AR in mesangium, reduction of oxidative stress, and amelioration of extracellular matrix synthesis and cell proliferation. Further studies are warranted to explore the role of AR in DN and the therapeutic implications by AR inhibitors such as BBR.

  16. H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells.

    PubMed

    Song, Guohua; Tian, Hua; Liu, Jia; Zhang, Hongle; Sun, Xuejun; Qin, Shucun

    2011-09-01

    H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-α. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H(2) in endothelial cells. H(2) significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-α, at the protein and mRNA levels. The TNF-α-induced upregulation of LOX-1 was also attenuated by the NF-κB inhibitor N-acetyl-L-cysteine. H(2) inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.

  17. A new and potent calmodulin antagonist, HF-2035, which inhibits vascular relaxation induced by nitric oxide synthase.

    PubMed

    Win, N H; Ishikawa, T; Saito, N; Kato, M; Yokokura, H; Watanabe, Y; Iida, Y; Hidaka, H

    1996-03-28

    HF-2035, 2-[N-(2-aminoethyl)-N-(2,4,5-trichlorobenzenesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, was synthesized and its effects on calmodulin-dependent enzymes were investigated. HF-2035 inhibited calmodulin kinase I, calmodulin kinase II and myosin light-chain kinase with IC50 values of 1.3 microM, 1.6 microM and 68 microM, respectively. HF-2035 also inhibited the activity of recombinant rat neuronal nitric oxide synthase, one of the calmodulin-dependent enzymes, with a Ki of 0.78 microM. Partially purified nitric oxide synthase of rat brain was also inhibited by HF-2035 with an IC50 of 3.2 microM. Kinetic analysis indicated that this inhibitory effect of HF-2035 was competitive with respect to calmodulin. We examined the effects of HF-2035 on constitutive nitric oxide synthase in a bioassay using vascular strips of rabbit carotid artery with and without endothelium. HF-2035 inhibited acetylcholine- and calcium ionophore, A23187 (6S-[6 alpha (2S*,3S*),8 beta (R*),9 beta, 11 alpha]-5- (methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)- ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazol ecarboxylic acid)-induced relaxation of endothelium-intact strips with an ED50 of 1.5 +/- 0.5 microM and 2.8 +/- 1 microM, respectively. This compound, however, did not inhibit N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A), an exogenous nitric oxide donor, -induced relaxation of endothelium-denuded strips. W-7 (N-(6-aminohexyl)-5-chloro-1- naphthalenesulfonamide) inhibited acetylcholine-induced relaxation with an ED50 of 46 +/- 7 microM, which was 30-fold less potent than HF-2035. HF-2035 was unable to inhibit the activity of the inducible form of nitric oxide synthase in isolated thoracic aorta of rat treated with Escherichia coli lipopolysaccharide. These findings suggest that HF-2035 is a new and potent calmodulin antagonist, and may be used as a mother compound to develop more selective inhibitors of constitutive nitric oxide

  18. Nitric oxide therapies for local inhibition of platelets' activitation on blood-contacting surfaces

    NASA Astrophysics Data System (ADS)

    Amoako, Kagya Agyeman

    Blood-contacting devices interact with blood during their function much like the endothelium that modulates hemostasis. The surfaces of these devices however, lack endothelial-like properties, and consequently, upon blood contact, activate clotting factors to form clots. Systemic heparinization for inhibiting clot formation can cause bleeding and surface coatings show insignificant benefits. This research investigated nitric oxide (NO) production mimicry of the endothehum on artificial lungs (ALs) and pediatric catheters. Their surfaces were functionalized either by (1) entrapping NO donors inside their bulk, (2) incorporating catalysts to generate NO from NO-donors or (3) supplementing NO into sweep gas of artificial lungs. Pediatric catheters functionalized with NO-donor thin coats using method 1 is limited by short NO release duration. Method 2 has not been applied to large surface-area, low-flow devices like the AL. In this work NO-generating silicone membranes were synthesized and characterized to determine the relationship between surface properties, NO flux, and blood clotting time. These outcomes helped develop and optimize NO-generating gas-exchange silicone fibers that represent the majority of ALs surface area. The first NO-generating AL prototypes, using those fibers, were manufactured, incorporated into NO-generating circuits and tested for their non-thrombogenicity. To test for NO-release duration and non-thrombogenicity, catheters were fabricated to incorporate NO-donors inside their walls, characterized for NO flux and release duration by chemilumincscence, and tested for patency using a thrombogenicity model in rabbits. Methods 1-2 involve material modification using complicated and expensive chemical formulations and/or manufacturing. Method 3 however, functionalizes ALs by only adding NO into sweep gas. Decade-long anti-clotting testing using a wide range of NO concentrations has been conducted without knowledge of what concentration yields

  19. Rutin inhibits oleic acid induced lipid accumulation via reducing lipogenesis and oxidative stress in hepatocarcinoma cells.

    PubMed

    Wu, Cheng-Hsun; Lin, Ming-Cheng; Wang, Hsueh-Chun; Yang, Mon-Yuan; Jou, Ming-Jia; Wang, Chau-Jong

    2011-03-01

    Excessive lipid accumulation within liver has been proposed to cause obesity, hyperlipidemia, diabetes, and fatty liver disease. Rutin, a common dietary flavonoid that is consumed in fruits, vegetables, and plant-derived beverages, has various biological functions, including antioxidant, anti-inflammatory, and anticancer effects. However, a hypolipidemic effect of rutin on fatty liver disease has not been reported. In this study, we examined the effect of rutin on reducing lipid accumulation in hepatic cells. Hepatocytes were treated with oleic acid (OA) containing with or without rutin to observe the lipid accumulation by Nile red stain. The result showed rutin suppressed OA-induced lipid accumulation and increased adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activity in hepatocytes. The expression of critical molecule involved in lipid synthesis, sterol regulatory element binding proteins-1 (SREBP-1), was attenuated in rutin-treated cells. Moreover, long-term incubation of rutin inhibited the transcriptions of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), glycerol-3-phosphate acyltransferase (GPAT), fatty acid synthase (FAS), and acetyl-coenzyme carboxylase (ACC). Besides, we also found out the antioxidative effect of rutin by increasing the expression of peroxisome proliferator-activated receptor (PPAR)-α and antioxidative enzymes. Taken together, our findings suggest rutin could attenuate lipid accumulation by decreasing lipogenesis and oxidative stress in hepatocyte.

  20. Sigma 1 receptor agonists act as neuroprotective drugs through inhibition of inducible nitric oxide synthase.

    PubMed

    Vagnerova, Kamila; Hurn, Patricia D; Bhardwaj, Anish; Kirsch, Jeffrey R

    2006-08-01

    Postischemic administration of the sigma-1 agonists reduces ischemic brain injury; however, the mechanism is unclear. We hypothesized that the sigma-1 agonist (+)isoform of pentazocine (P(+)) reduces damage in part by ameliorating cell death mediated via inducible nitric oxide synthase (iNOS) and that the (-)isoform (P(-)) lacks this effect. We compared treatment with P(+) with or without the iNOS inhibitor aminoguanidine (AG) and also the effects of P(+) in iNOS deficient (iNOSKO) mice. A possible mechanism of neuroprotection is inhibition of iNOS expression. Male C57/Bl6 mice were subjected to transient middle cerebral artery occlusion (90 min) and drugs were administered with reperfusion: 1) P(+) with AG (P+/AG), 2) P(+), 3) P(-), 4) AG, or 5) placebo. iNOSKOs were treated with either P(+) or placebo. Infarction (triphenyltetrazolium chloride histology, 72 h) was reduced by P(+) treatment in striatum by 44% and in neocortex by 23% versus placebo (P < 0.05), a reduction comparable to AG effect. P(-) did not attenuate brain injury. There was no difference in P(+)/AG treatment compared with showed the same level of neuroprotection as P(+) alone. P(+) also did not provide further neuroprotection for iNOSKOs. We conclude that postischemic administration of P(+) reduces infarct volume in mice. Because AG provides no additional benefit to P(+) treatment and iNOSKOs do not benefit from P(+), we speculate that P(+) acts by suppressing cell death resulting from iNOS toxicity.

  1. Thiol-modifying phenylarsine oxide inhibits guanine nucleotide binding of Rho but not of Rac GTPases.

    PubMed

    Gerhard, Ralf; John, Harald; Aktories, Klaus; Just, Ingo

    2003-06-01

    Phenylarsine oxide (PAO) is a phosphotyrosine phosphatase inhibitor that cross-links vicinal thiol groups, thereby inactivating phosphatases possessing XCysXXCysX motifs. The RhoA-GTPase, but not the Rac1-GTPase, also possesses vicinal cysteines within the guanine nucleotide-binding region (aa 13-20) and the phosphohydrolase activity site. Treatment of Caco-2 cells with PAO showed a dose-dependent reorganization of the actin cytoskeleton, indicating involvement of Rho GTPases. As tested by pull-down experiments, RhoA, but not Rac1, from cell lysates was inactivated by PAO in a concentration-dependent manner. Modification of RhoA by PAO resulted in altered mobility on SDS-polyacrylamide gel electrophoresis, and PAO-modified RhoA was no longer substrate for C3-catalyzed ADP-ribosylation. Furthermore, RhoA treated with PAO, but not Rac1 treated with PAO, lost its property to bind to guanine nucleotides. Matrix-assisted laser desorption ionization-mass analysis of PAO-modified RhoA showed a mass shift according to an adduction of a single PAO molecule per molecule RhoA. Further analysis of Glu-C-generated RhoA peptides confirmed binding of PAO to a peptide harboring the guanine nucleotide binding region. Thus, PAO does not exclusively inhibit phosphotyrosine phosphatases but also inactivates RhoA by alteration of nucleotide binding.

  2. Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression.

    PubMed

    Xiao, Yu-Feng; Li, Jian-Mei; Wang, Su-Min; Yong, Xin; Tang, Bo; Jie, Meng-Meng; Dong, Hui; Yang, Xiao-Chao; Yang, Shi-Ming

    2016-01-01

    Gastric cancer is one of the leading causes of tumor-related deaths in the world. Current treatment options do not satisfy doctors and patients, and new therapies are therefore needed. Cerium oxide nanoparticles (CNPs) have been studied as a potential therapeutic approach for treating many diseases. However, their effects on human gastric cancer are currently unknown. Therefore, in this study, we aimed to characterize the effects of CNPs on human gastric cancer cell lines (MKN28 and BGC823). Gastric cancer cells were cocultured with different concentrations of CNPs, and proliferation and migration were measured both in vitro and in vivo. We found that CNPs inhibited the migration of gastric cancer cells when applied at different concentrations, but only a relatively high concentration (10 µg/mL) of CNPs suppressed proliferation. Furthermore, we found that CNPs increased the expression of DHX15 and its downstream signaling pathways. We therefore provide evidence showing that CNPs may be a promising approach to suppress malignant activity of gastric cancer by increasing the expression of DHX15.

  3. Rat intestinal mast cell amines are released during nitric oxide synthase inhibition in vitro

    PubMed Central

    Northover, B. J.

    1996-01-01

    Inhibition of nitric oxide synthase increases microvascular permeability in rat small intestinal villi. To determine the mechanism(s) whereby this occurs we have perfused the vasculature of rat isolated small intestines with a gelatin-containing physiological salt solution. Inclusion of N-nitro-L-argintne methyl ester (L-NAME, 100 μM) or indomethacin (1 μM) in the perfusate increased leakage of injected colloidal carbon into microvessel walls. Pre-treatment with sodium nitroprusside (10 μM) significantly reduced the effects of both L-NAME and indomethacin, whereas carbacyclin (1 μM) only reduced the effects of indomethacin. PD151242 (1 μM) showed some antagonism towards the effects of L-NAME, but nordihydroguaiaretic acid (3 μM) was inactive. Pre-tment with cyproheptadine (10 μM) reduced the effects of both L-NAME and indomethacin, and also significantly reduced background (control) colloidal carbon leakage. Small intestines from polymixin B-treated rats showed significantly reduced colloidal carbon leakage in response to L-NAME. This suggests that the leakage-enhancing effects of both L-NAME and indomethacin in this preparation may be mediated by mast cell-derived amines. PMID:18475694

  4. Iron oxide nanoparticles induce Pseudomonas aeruginosa growth, induce biofilm formation, and inhibit antimicrobial peptide function†

    PubMed Central

    Borcherding, Jennifer; Baltrusaitis, Jonas; Chen, Haihan; Stebounova, Larissa; Wu, Chia-Ming; Rubasinghege, Gayan; Mudunkotuwa, Imali A.; Caraballo, Juan Carlos; Zabner, Joseph

    2014-01-01

    Given the increased use of iron-containing nanoparticles in a number of applications, it is important to understand any effects that iron-containing nanoparticles can have on the environment and human health. Since iron concentrations are extremely low in body fluids, there is potential that iron-containing nanoparticles may influence the ability of bacteria to scavenge iron for growth, affect virulence and inhibit antimicrobial peptide (AMP) function. In this study, Pseudomonas aeruginosa (PA01) and AMPs were exposed to iron oxide nanoparticles, hematite (α-Fe2O3), of different sizes ranging from 2 to 540 nm (2 ± 1, 43 ± 6, 85 ± 25 and 540 ± 90 nm) in diameter. Here we show that the greatest effect on bacterial growth, biofilm formation, and AMP function impairment is found when exposed to the smallest particles. These results are attributed in large part to enhanced dissolution observed for the smallest particles and an increase in the amount of bioavailable iron. Furthermore, AMP function can be additionally impaired by adsorption onto nanoparticle surfaces. In particular, lysozyme readily adsorbs onto the nanoparticle surface which can lead to loss of peptide activity. Thus, this current study shows that co-exposure of nanoparticles and known pathogens can impact host innate immunity. Therefore, it is important that future studies be designed to further understand these types of impacts. PMID:25221673

  5. Polyethylene oxide (PEO)-hyaluronic acid (HA) nanofibers with kanamycin inhibits the growth of Listeria monocytogenes.

    PubMed

    Ahire, J J; Robertson, D D; van Reenen, A J; Dicks, L M T

    2017-02-01

    Listeria monocytogenes is well known to cause prosthetic joint infections in immunocompromised patients. In this study, polyethylene oxide (PEO) nanofibers, containing kanamycin and hyaluronic acid (HA), were prepared by electrospinning at a constant electric field of 10kV. PEO nanofibers spun with 0.2% (w/v) HA and 1% (w/v) kanamycin had a smooth, bead-free structure at 30-35% relative humidity. The average diameter of the nanofibers was 83±20nm. Attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy indicated that kanamycin was successfully incorporated into PEO/HA matrix. The presence of kanamycin affects the thermal properties of PEO/HA nanofibers, as shown by differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The kanamycin-PEO-HA nanofibers (1mg; 47±3μg kanamycin) inhibited the growth of L. monocytogenes EDGe by 62%, as compared with PEO-HA nanofibers, suggesting that it may be used to coat prosthetic implants to prevent secondary infections.

  6. Increased hypoxic tolerance by chemical inhibition of oxidative phosphorylation: "chemical preconditioning".

    PubMed

    Riepe, M W; Esclaire, F; Kasischke, K; Schreiber, S; Nakase, H; Kempski, O; Ludolph, A C; Dirnagl, U; Hugon, J

    1997-03-01

    A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: "chemical preconditioning." The amplitude of CA1 population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31 +/- 27% (mean +/- SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1-24 h prior to slice preparation (preconditioned slices), psap improved to 90 +/- 15% (p < 0.01). Posthypoxic oxygen free radicals were reduced to 65 +/- 10% (mean +/- SD) of control in preconditioned slices (p < 0.05). Posthypoxic neuronal density improved from 52 +/- 15% (mean +/- SD) in control slices to 97 +/- 23% in preconditioned slices (p < 0.001). Glibenclamide, an antagonist at KATP-channels, partly reversed increased hypoxic tolerance. We conclude that chemical preconditioning induces early-onset long-lasting tolerance against in vitro hypoxia. Ultimately, this strategy may be applicable as a neuroprotective strategy in humans.

  7. Phenylarsine Oxide Inhibits the Fusicoccin-Induced Activation of Plasma Membrane H+-ATPase1

    PubMed Central

    Olivari, Claudio; Albumi, Cristina; Pugliarello, Maria Chiara; De Michelis, Maria Ida

    2000-01-01

    To investigate the mechanism by which fusicoccin (FC) induces the activation of the plasma membrane (PM) H+-ATPase, we used phenylarsine oxide (PAO), a known inhibitor of protein tyrosine-phosphatases. PAO was supplied in vivo in the absence or presence of FC to radish (Raphanus sativus L.) seedlings and cultured Arabidopsis cells prior to PM extraction. Treatment with PAO alone caused a slight decrease of PM H+-ATPase activity and, in radish, a decrease of PM-associated 14-3-3 proteins. When supplied prior to FC, PAO drastically inhibited FC-induced activation of PM H+-ATPase, FC binding to the PM, and the FC-induced increase of the amount of 14-3-3 associated with the PM. On the contrary, PAO was completely ineffective on all of the above-mentioned parameters when supplied after FC. The H+-ATPase isolated from PAO-treated Arabidopsis cells maintained the ability to respond to FC if supplied with exogenous, nonphosphorylated 14-3-3 proteins. Altogether, these results are consistent with a model in which the dephosphorylated state of tyrosine residues of a protein(s), such as 14-3-3 protein, is required to permit FC-induced association between the 14-3-3 protein and the PM H+-ATPase. PMID:10677439

  8. Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats.

    PubMed

    Schober, Gudrun; Arnold, Myrtha; Birtles, Susan; Buckett, Linda K; Pacheco-López, Gustavo; Turnbull, Andrew V; Langhans, Wolfgang; Mansouri, Abdelhak

    2013-05-01

    Acyl CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final step in triacylglycerol (TAG) synthesis and is highly expressed in the small intestine. Because DGAT-1 knockout mice are resistant to diet-induced obesity, we investigated the acute effects of intragastric (IG) infusion of a small molecule diacylglycerol acyltransferase-1 inhibitor (DGAT-1i) on eating, circulating fat metabolites, indirect calorimetry, and hepatic and intestinal expression of key fat catabolism enzymes in male rats adapted to an 8 h feeding-16 h deprivation schedule. Also, the DGAT-1i effect on fatty acid oxidation (FAO) was investigated in enterocyte cell culture models. IG DGAT-1i infusions reduced energy intake compared with vehicle in high-fat diet (HFD)-fed rats, but scarcely in chow-fed rats. IG DGAT-1i also blunted the postprandial increase in serum TAG and increased β-hydroxybutyrate levels only in HFD-fed rats, in which it lowered the respiratory quotient and increased intestinal, but not hepatic, protein levels of Complex III of the mitochondrial respiratory chain and of mitochondrial hydroxymethylglutaryl-CoA synthase. Finally, the DGAT-1i enhanced FAO in CaCo2 (EC50 = 0.3494) and HuTu80 (EC50 = 0.00762) cells. Thus, pharmacological DGAT-1 inhibition leads to an increase in intestinal FAO and ketogenesis when dietary fat is available. This may contribute to the observed eating-inhibitory effect.

  9. Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production

    PubMed Central

    Alfajaro, Mia Madel; Choi, Jong-Soon; Kim, Deok-Song; Seo, Ja-Young; Kim, Ji-Yun; Park, Jun-Gyu; Soliman, Mahmoud; Baek, Yeong-Bin; Cho, Eun-Hyo; Kwon, Joseph; Kwon, Hyung-Jun; Park, Su-Jin; Lee, Woo Song; Kang, Mun-Il; Hosmillo, Myra

    2016-01-01

    ABSTRACT Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. IMPORTANCE Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E2 (PGE2

  10. Driven shielding capacitive proximity sensor

    NASA Technical Reports Server (NTRS)

    Vranish, John M. (Inventor); McConnell, Robert L. (Inventor)

    2000-01-01

    A capacitive proximity sensing element, backed by a reflector driven at the same voltage as and in phase with the sensor, is used to reflect the field lines away from a grounded robot arm towards an intruding object, thus dramatically increasing the sensor's range and sensitivity.

  11. IkappaB is a sensitive target for oxidation by cell-permeable chloramines: inhibition of NF-kappaB activity by glycine chloramine through methionine oxidation.

    PubMed

    Midwinter, Robyn G; Cheah, Fook-Choe; Moskovitz, Jackob; Vissers, Margret C; Winterbourn, Christine C

    2006-05-15

    Hypochlorous acid (HOCl) is produced by the neutrophil enzyme, myeloperoxidase, and reacts with amines to generate chloramines. These oxidants react readily with thiols and methionine and can affect cell-regulatory pathways. In the present study, we have investigated the ability of HOCl, glycine chloramine (Gly-Cl) and taurine chloramine (Tau-Cl) to oxidize IkappaBalpha, the inhibitor of NF-kappaB (nuclear factor kappaB), and to prevent activation of the NF-kappaB pathway in Jurkat cells. Glycine chloramine (Gly-Cl) and HOCl were permeable to the cells as determined by oxidation of intracellular GSH and inactivation of glyceraldehyde-3-phosphate dehydrogenase, whereas Tau-Cl showed no detectable cell permeability. Both Gly-Cl (20-200 muM) and HOCl (50 microM) caused oxidation of IkappaBalpha methionine, measured by a shift in electrophoretic mobility, when added to the cells in Hanks buffer. In contrast, a high concentration of Tau-Cl (1 mM) in Hanks buffer had no effect. However, Tau-Cl in full medium did modify IkappaBalpha. This we attribute to chlorine exchange with other amines in the medium to form more permeable chloramines. Oxidation by Gly-Cl prevented IkappaBalpha degradation in cells treated with TNFalpha (tumour necrosis factor alpha) and inhibited nuclear translocation of NF-kappaB. IkappaBalpha modification was reversed by methionine sulphoxide reductase, with both A and B forms required for complete reduction. Oxidized IkappaBalpha persisted intracellularly for up to 6 h. Reversion occurred in the presence of cycloheximide, but was prevented if thioredoxin reductase was inhibited, suggesting that it was due to endogenous methionine sulphoxide reductase activity. These results show that cell-permeable chloramines, either directly or when formed in medium, could regulate NF-kappaB activation via reversible IkappaBalpha oxidation.

  12. Selective Inhibition of Ammonium Oxidation and Nitrification-Linked N2O Formation by Methyl Fluoride and Dimethyl Ether

    PubMed Central

    Miller, Laurence G.; Coutlakis, M. Denise; Oremland, Ronald S.; Ward, Bess B.

    1993-01-01

    Methyl fluoride (CH3F) and dimethyl ether (DME) inhibited nitrification in washed-cell suspensions of Nitrosomonas europaea and in a variety of oxygenated soils and sediments. Headspace additions of CH3F (10% [vol/vol]) and DME (25% [vol/vol]) fully inhibited NO2- and N2O production from NH4+ in incubations of N. europaea, while lower concentrations of these gases resulted in partial inhibition. Oxidation of hydroxylamine (NH2OH) by N. europaea and oxidation of NO2- by a Nitrobacter sp. were unaffected by CH3F or DME. In nitrifying soils, CH3F and DME inhibited N2O production. In field experiments with surface flux chambers and intact cores, CH3F reduced the release of N2O from soils to the atmosphere by 20- to 30-fold. Inhibition by CH3F also resulted in decreased NO3- + NO2- levels and increased NH4+ levels in soils. CH3F did not affect patterns of dissimilatory nitrate reduction to ammonia in cell suspensions of a nitrate-respiring bacterium, nor did it affect N2O metabolism in denitrifying soils. CH3F and DME will be useful in discriminating N2O production via nitrification and denitrification when both processes occur and in decoupling these processes by blocking NO2- and NO3- production. PMID:16349011

  13. Selective inhibition of ammonium oxidation and nitrification-linked N2O formation by methyl fluoride and dimethyl ether

    USGS Publications Warehouse

    Miller, L.G.; Coutlakis, M.D.; Oremland, R.S.; Ward, B.B.

    1993-01-01

    Methyl fluoride (CH3F) and dimethyl ether (DME) inhibited nitrification in washed-cell suspensions of Nitrosomonas europaea and in a variety of oxygenated soils and sediments. Headspace additions of CH3F (10% [vol/vol]) and DME (25% [vol/vol]) fully inhibited NO2- and N2O production from NH4+ in incubations of N. europaea, while lower concentrations of these gases resulted in partial inhibition. Oxidation of hydroxylamine (NH2OH) by N. europaea and oxidation of NO2- by a Nitrobacter sp. were unaffected by CH3F or DME. In nitrifying soils, CH3F and DME inhibited N2O production. In field experiments with surface flux chambers and intact cores, CH3F reduced the release of N2O from soils to the atmosphere by 20- to 30-fold. Inhibition by CH3F also resulted in decreased NO3- + NO2- levels and increased NH4+ levels in soils. CH3F did not affect patterns of dissimilatory nitrate reduction to ammonia in cell suspensions of a nitrate- respiring bacterium, nor did it affect N2O metabolism in denitrifying soils. CH3F and DME will be useful in discriminating N2O production via nitrification and denitrification when both processes occur and in decoupling these processes by blocking NO2- and NO3- production.

  14. Capacitive Proximity Sensor Has Longer Range

    NASA Technical Reports Server (NTRS)

    Vranish, John M.

    1992-01-01

    Capacitive proximity sensor on robot arm detects nearby object via capacitive effect of object on frequency of oscillator. Sensing element part of oscillator circuit operating at about 20 kHz. Total capacitance between sensing element and ground constitutes tuning capacitance of oscillator. Sensor circuit includes shield driven by replica of alternating voltage applied to sensing element. Driven shield concentrates sensing electrostatic field in exterior region to enhance sensitivity to object. Sensitivity and dynamic range has corresponding 12-to-1 improvement.

  15. Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-01

    Hesperidin methyl chalcone (HMC) is a safe flavonoid used to treat chronic venous diseases, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress have never been described in vivo. Thus, the purpose of this study was to evaluate the effects of systemic administration of HMC in skin oxidative stress and inflammation induced by UVB irradiation. To induce skin damage, hairless mice were exposed to an acute UVB irradiation dose of 4.14 J/cm(2), and the dorsal skin samples were collected to evaluate oxidative stress and inflammatory response. The intraperitoneal treatment with HMC at the dose of 300 mg/kg inhibited UVB irradiation-induced skin edema, neutrophil recruitment, and matrix metalloproteinase-9 activity. HMC also protected the skin from UVB irradiation-induced oxidative stress by maintaining ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability and antioxidant levels (reduced glutathione and catalase). Corroborating, HMC inhibited UVB irradiation-induced superoxide anion generation and gp91phox (NADPH oxidase subunit) mRNA expression. Furthermore, the antioxidant effect of HMC resulted in lower production of inflammatory mediators, including lipid hydroperoxides and a wide range of cytokines. Taken together, these results unveil a novel applicability of HMC in the treatment of UVB irradiation-induced skin inflammation and oxidative stress.

  16. Inhibition of human low-density lipoprotein oxidation in vitro by Maharishi Ayur-Veda herbal mixtures.

    PubMed

    Sharma, H M; Hanna, A N; Kauffman, E M; Newman, H A

    1992-12-01

    In this study, we examined the effect of the Maharishi Ayur-Veda herbal mixtures (MAHMs) Maharishi Amrit Kalash-4 and -5 (M-4 and M-5), MA-631, and Maharishi Coffee Substitute (MCS) on low-density lipoprotein (LDL) oxidation and compared the potency of these mixtures to ascorbic acid, alpha-tocopherol, and probucol. LDL was incubated in 95% air and 5% CO2, with or without 3 microM Cu(+2), in the presence or absence of MAHMs, for 6 or 24 h. In a separate experiment, LDL was incubated as above except MAHMs were added at 0, 1.5, and 3.5 h after incubation started to assess their effect on initiation and propagation of LDL oxidation. Our results demonstrate that MAHMs caused concentration-dependent inhibition of LDL oxidation as assessed by thiobarbituric acid-reactive substances and electrophoretic mobility. The MAHM showed more antioxidant potency in preventing LDL oxidation than ascorbic acid, alpha-tocopherol, or probucol. Also, MAHMs inhibited both initiation and propagation of cupric ion-catalyzed LDL oxidation. These results suggest the importance of further research on these herbal mixtures in the investigation of atherosclerosis and free radical-induced injury.

  17. Curcumin protects human adipose-derived mesenchymal stem cells against oxidative stress-induced inhibition of osteogenesis.

    PubMed

    Wang, Nan; Wang, Feng; Gao, Youshui; Yin, Peipei; Pan, Chenhao; Liu, Wei; Zhou, Zubin; Wang, Jiaxiang

    2016-11-01

    The detrimental effects of oxidative stress on the skeletal system have been documented, and understanding the mechanisms is important to design a therapeutic strategy. As an antioxidant and anti-inflammatory agent, the active ingredient of turmeric curcumin has been used as medication for numerous complications including bone loss. However, it is unclear if curcumin could influence the osteogenic potential of mesenchymal stem cells (MSCs), particularly in oxidative injuries. Here we demonstrate that curcumin treatment protects cell death caused by hydrogen peroxide (H2O2) exposure in human adipose-derived MSCs in vitro. Importantly, curcumin is able to enhance the osteoblast differentiation of human adipose-derived MSCs that is inhibited by H2O2. Notably, both oxidative stress and the inhibition of Wnt/β-catenin signaling are attenuated by curcumin treatment. These results suggest that curcumin can promote osteoblast differentiation of MSCs and protect the inhibitory effect elicited by oxidative injury. The findings support potential use of curcumin or related antioxidants in MSC-based bone regeneration for disease related with oxidative stress-induced bone loss.

  18. Pilot testing of sodium thiosulfate for oxidation/scaling inhibition in lime/limestone flue gas desulfurization systems

    SciTech Connect

    Chang, J.C.S.; Brna, T.G.

    1985-01-01

    Pilot plant tests have been conducted to evaluate sodium thiosulfate as an oxidation inhibition additive in five lime/limestone slurry flue gas desulfurization processes. It was found that the oxidation rate of absorbed sulfur dioxide (SO/sub 2/) was reduced by more than 50 percent in the presence of 100 to 200 ppm of thiosulfate ion in the scrubbing slurry. Calcium sulfate dihydrate (gypsum) scaling was eliminated and the unsaturated (with respect to gypsum) operation mode was maintained by the addition of sodium thiosulfate. Other benefits of sodium thiosulfate addition observed at the pilot plant included improvement in solids dewatering properties for limestone processes.

  19. Hydrogen Sulfide Inhibits High-Salt Diet-Induced Myocardial Oxidative Stress and Myocardial Hypertrophy in Dahl Rats

    PubMed Central

    Huang, Pan; Shen, Zhizhou; Yu, Wen; Huang, Yaqian; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2017-01-01

    The study aimed to examine the protective effect of hydrogen sulfide (H2S) on high-salt-induced oxidative stress and myocardial hypertrophy in salt-sensitive (Dahl) rats. Thirty male Dahl rats and 40 SD rats were included in the study. They were randomly divided into Dahl control (Dahl + NS), Dahl high salt (Dahl + HS), Dahl + HS + NaHS, SD + NS, SD + HS, SD + HS + NaHS, and SD + HS + hydroxylamine (HA). Rats in Dahl + NS and SD + NS groups were given chow with 0.5% NaCl and 0.9% normal saline intraperitoneally daily. Myocardial structure, α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) expressions were determined. Endogenous myocardial H2S pathway and oxidative stress in myocardial tissues were tested. Myocardial H2S pathway was downregulated with myocardial hypertrophy featured by increased heart weight/body weight and cardiomyocytes cross-sectional area, decreased α-MHC and increased β-MHC expressions in Dahl rats with high-salt diet (all P < 0.01), and oxidative stress in myocardial tissues was significantly activated, demonstrated by the increased contents of hydroxyl radical, malondialdehyde and oxidized glutathione and decreased total antioxidant capacity, carbon monoxide, catalase, glutathione, glutathione peroxidase, superoxide dismutase (SOD) activities and decreased SOD1 and SOD2 protein expressions (P < 0.05, P < 0.01). However, H2S reduced myocardial hypertrophy with decreased heart weight/body weight and cardiomyocytes cross-sectional area, increased α-MHC, decreased β-MHC expressions and inhibited oxidative stress in myocardial tissues of Dahl rats with high-salt diet. However, no significant difference was found in H2S pathway, myocardial structure, α-MHC and β-MHC protein and oxidative status in myocardial tissues among SD + NS, SD + HS, and SD + HS + NaHS groups. HA, an inhibitor of cystathionine β-synthase, inhibited myocardial H2S pathway (P < 0.01), and stimulated myocardial hypertrophy and oxidative stress in SD rats

  20. Hydrogen Sulfide Inhibits High-Salt Diet-Induced Myocardial Oxidative Stress and Myocardial Hypertrophy in Dahl Rats.

    PubMed

    Huang, Pan; Shen, Zhizhou; Yu, Wen; Huang, Yaqian; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2017-01-01

    The study aimed to examine the protective effect of hydrogen sulfide (H2S) on high-salt-induced oxidative stress and myocardial hypertrophy in salt-sensitive (Dahl) rats. Thirty male Dahl rats and 40 SD rats were included in the study. They were randomly divided into Dahl control (Dahl + NS), Dahl high salt (Dahl + HS), Dahl + HS + NaHS, SD + NS, SD + HS, SD + HS + NaHS, and SD + HS + hydroxylamine (HA). Rats in Dahl + NS and SD + NS groups were given chow with 0.5% NaCl and 0.9% normal saline intraperitoneally daily. Myocardial structure, α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) expressions were determined. Endogenous myocardial H2S pathway and oxidative stress in myocardial tissues were tested. Myocardial H2S pathway was downregulated with myocardial hypertrophy featured by increased heart weight/body weight and cardiomyocytes cross-sectional area, decreased α-MHC and increased β-MHC expressions in Dahl rats with high-salt diet (all P < 0.01), and oxidative stress in myocardial tissues was significantly activated, demonstrated by the increased contents of hydroxyl radical, malondialdehyde and oxidized glutathione and decreased total antioxidant capacity, carbon monoxide, catalase, glutathione, glutathione peroxidase, superoxide dismutase (SOD) activities and decreased SOD1 and SOD2 protein expressions (P < 0.05, P < 0.01). However, H2S reduced myocardial hypertrophy with decreased heart weight/body weight and cardiomyocytes cross-sectional area, increased α-MHC, decreased β-MHC expressions and inhibited oxidative stress in myocardial tissues of Dahl rats with high-salt diet. However, no significant difference was found in H2S pathway, myocardial structure, α-MHC and β-MHC protein and oxidative status in myocardial tissues among SD + NS, SD + HS, and SD + HS + NaHS groups. HA, an inhibitor of cystathionine β-synthase, inhibited myocardial H2S pathway (P < 0.01), and stimulated myocardial hypertrophy and oxidative stress in SD rats

  1. Capacitance Property of a Resonant Tunneling Diode

    NASA Astrophysics Data System (ADS)

    Sheng, Hanyu; Chua, Soo-Jin; Sinkkonen, Juha

    A simple capacitance formula based on a semiclassical electron transport theory is given. The results show that the charges stored in the quantum well of a resonant tunneling diode have a considerable effect on the capacitance in the resonant region. The calculated capacitance is consistent with the experimental results.

  2. Active Targets For Capacitive Proximity Sensors

    NASA Technical Reports Server (NTRS)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

    Lightweight, low-power active targets devised for use with improved capacitive proximity sensors described in "Capacitive Proximity Sensor Has Longer Range" (GSC-13377), and "Capacitive Proximity Sensors With Additional Driven Shields" (GSC-13475). Active targets are short-distance electrostatic beacons; they generate known alternating electro-static fields used for alignment and/or to measure distances.

  3. Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice.

    PubMed

    Abdel-Zaher, Ahmed O; Mostafa, Mostafa G; Farghly, Hanan M; Hamdy, Mostafa M; Omran, Ghada A; Al-Shaibani, Najlaà K M

    2013-02-28

    In this study, the effect of thymoquinone on morphine-induced tolerance and dependence in mice was investigated. Repeated administration of thymoquinone along with morphine attenuated the development of morphine tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone-precipitated withdrawal manifestations. Concurrently, morphine-induced progressive increase in brain malondialdehyde (MDA) level and nitric oxide (NO) production as well as progressive decrease in brain intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity were inhibited by co-administration of thymoquinone. Morphine-induced progressive increase in brain glutamate level was not inhibited by concomitant administration of thymoquinone. Similarly, co-administration of thymoquinone inhibited naloxone-induced increase in brain MDA level, NO overproduction and decrease in brain intracellular GSH level and GSH-Px activities but it did not inhibit naloxone-induced elevation of brain glutamate level in morphine-dependent mice. The inhibitory effect of thymoquinone on morphine-induced tolerance and dependence on naloxone-induced biochemical alterations in morphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine, the antioxidant, N-acetylcysteine or the NO synthase inhibitor, L-N (G)-nitroarginine methyl ester. On the other hand, this inhibitory effect of thymoquinone was antagonized by concurrent i.p. administration of NO precursor, L-arginine. In addition, concomitant administration of thymoquinone inhibited morphine tolerance and dependence-induced increase in inducible but not in neuronal NO synthase mRNA expression in mice brain. These results demonstrate that inhibition of morphine-induced oxidative stress, increase in the expression of brain inducible NO synthase and NO overproduction by thymoquinone can attenuate the development of morphine tolerance and dependence.

  4. P2X Receptors Inhibit NaCl Absorption in mTAL Independently of Nitric Oxide

    PubMed Central

    Svendsen, Samuel L.; Isidor, Søren; Praetorius, Helle A.; Leipziger, Jens

    2017-01-01

    Activation of basolateral P2X receptors markedly reduces NaCl absorption in mouse medullary thick ascending limb (mTAL). Here we tested the role of nitric oxide (NO) in the ATP-mediated (P2X) transport inhibition. We used isolated, perfused mTALs from mice to electrically measure NaCl absorption. By microelectrodes we determined the transepithelial voltage (Vte) and transepithelial resistance (Rte). Via these two parameters, we calculated the equivalent short circuit current, I'sc as a measure of the transepithelial Na+ absorption. Basolateral ATP (100 μM) acutely induced reversible inhibition of Na+ absorption (24 ± 4%, n = 10). Addition of L-arginine (100 μM) had no apparent effect on the ATP-induced transport inhibition. Acute reduction of extracellular [Ca2+] to either 100 nM or 0 nM by addition of EGTA had no effect on the ATP-induced transport inhibition. In the presence of the NO synthase (NOS) inhibitor L-NAME (100 μM) and/or ODQ to inhibit the guanylyl cyclase, the ATP effect remained unaffected. Increasing the concentration and incubation time for L-NAME (1 mM) still did not reveal any effect on the ATP-mediated transport inhibition. Acute addition of the NO donors SNAP (100 μM) and Spermine NONOate (10 μM) did not alter tubular transport. High concentrations of L-NAME (1 mM) in itself, however, reduced the transepithelial transport significantly. Thus, we find no evidence for nitric oxide (NO) as second messenger for P2X receptor-dependent transport inhibition in mTAL. Moreover, Ca2+ signaling appears not involved in the ATP-mediated effect. It remains undefined how P2X receptors trigger the marked reduction of transport in the TAL. PMID:28174542

  5. Inhibition of ornithine decarboxylase potentiates nitric oxide production in LPS-activated J774 cells

    PubMed Central

    Baydoun, Anwar R; Morgan, David M L

    1998-01-01

    We have examined whether modulation of the polyamine biosynthetic pathway, through inhibition by α-difluoromethylornithine (DFMO) of the rate limiting enzyme, ornithine decarboxylase (ODC), modulates NO synthesis in J774 macrophages.DFMO potentiated LPS-stimulated nitrite production in both a concentration- and time-dependent manner, increasing nitrite levels by 48±5% at 10 mM. This effect was observed in cells pre-treated with DFMO for 24 h prior to stimulation with LPS. Addition of DFMO 12 h after LPS failed to potentiate LPS-induced nitrite production.Supplementation of the culture medium with horse serum (10%) in place of foetal calf serum (10%) caused no significant change in either LPS-induced nitrite production or in the ability of DFMO (10  mM) to potentiate LPS-induced NO synthesis.Metabolism of L-[3H]arginine to L-[3H]citrulline by partially purified inducible nitric oxide synthase (iNOS) was not significantly altered by either DFMO (1–10 mM) or by putrescine (0.001–1 mM), spermidine (0.001–1 mM) or spermine (0.001–1 mM). iNOS activity was also unaffected by 1 mM EGTA but was markedly attenuated (70±0.07%) by L-NMMA (100 μM).Pre-incubation of cells with DFMO (10 mM; 24 h) prior to activation with LPS resulted in enhanced (∼2 fold) iNOS protein expression.These results show that DFMO potentiates LPS-induced nitrite production in the murine macrophage cell line J774. Since the only known mechanism of action of DFMO is inhibition of ODC, and thus polyamine biosynthesis, we conclude that expression of iNOS can be critically regulated by endogenous polyamines. PMID:9884080

  6. Inhibition of nitric oxide synthase enhances superoxide activity in canine kidney.

    PubMed

    Majid, Dewan S A; Nishiyama, Akira; Jackson, Keith E; Castillo, Alexander

    2004-07-01

    To evaluate the role of a potential interaction between superoxide anion (O(2)(-)) and nitric oxide (NO) in regulating kidney function, we examined the renal responses to intra-arterial infusion of a superoxide dismutase mimetic, tempol (0.5 mg.kg(-1).min(-1)), in anesthetized dogs treated with or without NO synthase inhibitor, N(omega)-nitro-l-arginine (NLA; 50 microg.kg(-1).min(-1)). In one group of dogs (n = 10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 +/- 0.4 to 5.0 +/- 0.4 ml.min(-1).g(-1)), glomerular filtration rate (GFR; 0.79 +/- 0.04 to 0.77 +/- 0.04 ml.min(-1).g(-1)), urine flow (V; 13.6 +/- 2.1 to 13.9 +/- 2.5 microl.min(-1).g(-1)), or sodium excretion (U(Na)V; 2.4 +/- 0.3 to 2.2 +/- 0.3 micromol.min(-1).g(-1)). Interestingly, when tempol was infused in another group of dogs (n = 12) pretreated with NLA, it caused increases in V (4.4 +/- 0.4 to 9.7 +/- 1.4 microl.min(-1).g(-1)) and in U(Na)V (0.7 +/- 0.1 to 1.3 +/- 0.2 micromol.min(-1).g(-1)) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 +/- 5 vs. 26 +/- 4%) and antinatriuretic (67 +/- 4 vs. 45 +/- 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 +/- 2.7 to 22.8 +/- 3.6 pg.min(-1).g(-1); n = 7), which returned to the control levels (11.6 +/- 3.4 pg.min(-1).g(-1)) during coadministration of tempol. These data suggest that NO synthase inhibition causes enhancement of endogenous O(2)(-) levels and support the hypothesis that NO plays a protective role against the actions of O(2)(-) in the kidney.

  7. Effects of chronic nitric oxide synthase inhibition on responses to acute exercise in swine.

    PubMed

    McAllister, Richard M; Newcomer, Sean C; Pope, Eric R; Turk, James R; Laughlin, M Harold

    2008-01-01

    Nitric oxide (NO) is potentially involved in several responses to acute exercise. We tested the hypotheses that inhibition of NO formation reduces maximal O(2) delivery to muscle, but does not affect O(2) utilization by muscle, therefore lowering maximal O(2) consumption. To test these hypotheses, swine (approximately 30 kg) drank either tap water (Con, n = 25) or water with N(G)-nitro-l-arginine methyl ester (8.0 +/- 0.4 mg x kg(-1) x day(-1) for >or=4 wk; LN, n = 24). Treatment efficacy was reflected by higher mean arterial pressure and lower plasma NO metabolite concentration in LN than Con (both P < 0.05). Swine completed two graded treadmill running tests to maximum. In the first test, O(2) consumption was determined at rest through maximal exercise intensity. O(2) consumption did not differ between groups at rest or at most exercise intensities, including maximum (Con, 40.8 +/- 1.8 ml x min(-1) x kg(-1); LN, 40.4 +/- 2.9; not significant). In the second test, tissue-specific blood flows were determined using the radiolabeled-microsphere technique. At rest, blood flows were lower (P < 0.05) in LN compared with Con for a number of tissues, including kidney, adrenal, lung, and several skeletal muscles. During both submaximal and maximal exercise, however, blood flows were similar between Con and LN for all 16 muscles examined; only blood flows to kidney (Con, 99 +/- 16 ml x min(-1) x 100 g; LN, 55 +/- 15; P < 0.05) and pancreas (Con, 25 +/- 7; LN, 6 +/- 2; P < 0.05) were lower in LN at maximum. Endothelium-dependent, but not -independent, relaxation of renal arterial segments was reduced (P < 0.05) in vitro. These data indicate that exercise-induced increases in muscle blood flows are maintained with chronic inhibition of NO formation and that maximal O(2) consumption is therefore preserved. Redundant vasodilatory pathways and/or upregulation of these pathways may underlie these findings.

  8. Effects of chronic nitric oxide synthase inhibition on responses to acute exercise in swine

    PubMed Central

    McAllister, Richard M.; Newcomer, Sean C.; Pope, Eric R.; Turk, James R.; Laughlin, M. Harold

    2012-01-01

    Nitric oxide (NO) is potentially involved in several responses to acute exercise. We tested the hypotheses that inhibition of NO formation reduces maximal O2 delivery to muscle, but does not affect O2 utilization by muscle, therefore lowering maximal O2 consumption. To test these hypotheses, swine (~30 kg) drank either tap water (Con, n = 25) or water with NG-nitro-L-arginine methyl ester (8.0 ± 0.4 mg · kg−1 · day−1 for ≥4 wk; LN, n = 24). Treatment efficacy was reflected by higher mean arterial pressure and lower plasma NO metabolite concentration in LN than Con (both P < 0.05). Swine completed two graded treadmill running tests to maximum. In the first test, O2 consumption was determined at rest through maximal exercise intensity. O2 consumption did not differ between groups at rest or at most exercise intensities, including maximum (Con, 40.8 ± 1.8 ml · min−1 · kg−1; LN, 40.4 ± 2.9; not significant). In the second test, tissue-specific blood flows were determined using the radiolabeled-microsphere technique. At rest, blood flows were lower (P < 0.05) in LN compared with Con for a number of tissues, including kidney, adrenal, lung, and several skeletal muscles. During both submaximal and maximal exercise, however, blood flows were similar between Con and LN for all 16 muscles examined; only blood flows to kidney (Con, 99 ± 16 ml · min−1 · 100 g; LN, 55 ± 15; P < 0.05) and pancreas (Con, 25 ± 7; LN, 6 ± 2; P < 0.05) were lower in LN at maximum. Endothelium-dependent, but not -independent, relaxation of renal arterial segments was reduced (P < 0.05) in vitro. These data indicate that exercise-induced increases in muscle blood flows are maintained with chronic inhibition of NO formation and that maximal O2 consumption is therefore preserved. Redundant vasodilatory pathways and/or upregulation of these pathways may underlie these findings. PMID:17975123

  9. Plasma lipid oxidation induced by peroxynitrite, hypochlorite, lipoxygenase and peroxyl radicals and its inhibition by antioxidants as assessed by diphenyl-1-pyrenylphosphine

    PubMed Central

    Morita, Mayuko; Naito, Yuji; Yoshikawa, Toshikazu; Niki, Etsuo

    2016-01-01

    Lipid oxidation has been implicated in the pathogenesis of many diseases. Lipids are oxidized in vivo by several different oxidants to give diverse products, in general lipid hydroperoxides as the major primary product. In the present study, the production of lipid hydroperoxides in the oxidation of mouse plasma induced by multiple oxidants was measured using diphenyl-1-pyrenylphosphine (DPPP) as a probe. DPPP itself is not fluorescent, but it reacts with lipid hydroperoxides stochiometrically to give highly fluorescent DPPP oxide and lipid hydroxides. The production of lipid hydroperoxides could be followed continuously in the oxidation of plasma induced by peroxynitrite, hypochlorite, 15-lipoxygenase, and peroxyl radicals with a microplate reader. A clear lag phase was observed in the plasma oxidation mediated by aqueous peroxyl radicals and peroxynitrite, but not in the oxidation induced by hypochlorite and lipoxygenase. The effects of several antioxidants against lipid oxidation induced by the above oxidants were assessed. The efficacy of antioxidants was dependent markedly on the type of oxidants. α-Tocopherol exerted potent antioxidant effects against peroxyl radical-mediated lipid peroxidation, but it did not inhibit lipid oxidation induced by peroxynitrite, hypochlorite, and 15-lipoxygenase efficiently, suggesting that multiple antioxidants with different selectivities are required for the inhibition of plasma lipid oxidation in vivo. This is a novel, simple and most high throughput method to follow plasma lipid oxidation induced by different oxidants and also to assess the antioxidant effects in biologically relevant settings. PMID:26774081

  10. Plasma lipid oxidation induced by peroxynitrite, hypochlorite, lipoxygenase and peroxyl radicals and its inhibition by antioxidants as assessed by diphenyl-1-pyrenylphosphine.

    PubMed

    Morita, Mayuko; Naito, Yuji; Yoshikawa, Toshikazu; Niki, Etsuo

    2016-08-01

    Lipid oxidation has been implicated in the pathogenesis of many diseases. Lipids are oxidized in vivo by several different oxidants to give diverse products, in general lipid hydroperoxides as the major primary product. In the present study, the production of lipid hydroperoxides in the oxidation of mouse plasma induced by multiple oxidants was measured using diphenyl-1-pyrenylphosphine (DPPP) as a probe. DPPP itself is not fluorescent, but it reacts with lipid hydroperoxides stochiometrically to give highly fluorescent DPPP oxide and lipid hydroxides. The production of lipid hydroperoxides could be followed continuously in the oxidation of plasma induced by peroxynitrite, hypochlorite, 15-lipoxygenase, and peroxyl radicals with a microplate reader. A clear lag phase was observed in the plasma oxidation mediated by aqueous peroxyl radicals and peroxynitrite, but not in the oxidation induced by hypochlorite and lipoxygenase. The effects of several antioxidants against lipid oxidation induced by the above oxidants were assessed. The efficacy of antioxidants was dependent markedly on the type of oxidants. α-Tocopherol exerted potent antioxidant effects against peroxyl radical-mediated lipid peroxidation, but it did not inhibit lipid oxidation induced by peroxynitrite, hypochlorite, and 15-lipoxygenase efficiently, suggesting that multiple antioxidants with different selectivities are required for the inhibition of plasma lipid oxidation in vivo. This is a novel, simple and most high throughput method to follow plasma lipid oxidation induced by different oxidants and also to assess the antioxidant effects in biologically relevant settings.

  11. Physiological state, growth mode, and oxidative stress play a role in Cd(II)-mediated inhibition of Nitrosomonas europaea 19718.

    PubMed

    Chandran, Kartik; Love, Nancy G

    2008-04-01

    The goal of this study was to determine the impact of physiological growth states (batch exponential and batch stationary growth) and growth modes (substrate-limited chemostat, substrate-sufficient exponential batch, and substrate-depleted stationary batch growth) on several measures of growth and responses to Cd(II)-mediated inhibition of Nitrosomonas europaea strain 19718. The specific oxygen uptake rate (sOUR) was the most sensitive indicator of inhibition among the different responses analyzed, including total cell abundance, membrane integrity, intracellular 16S rRNA/DNA ratio, and amoA expression. This observation remained true irrespective of the physiological state, the growth mode, or the mode of Cd(II) exposure. Based on the sOUR, a strong time-dependent exacerbation of inhibition (in terms of an inhibition coefficient [K(i)]) in exponential batch cultures was observed. Long-term inhibition levels (based on K(i) estimates) in metabolically active chemostat and exponential batch cultures were also especially severe and comparable. In contrast, the inhibition level in stationary-phase cultures was 10-fold lower and invariable with exposure time. Different strategies for surviving substrate limitation (a 10-fold increase in amoA expression) and starvation (the retention of 16S rRNA levels) in N. europaea cultures were observed. amoA expression was most negatively impacted by Cd(II) exposure in the chemostat cultures, was less impacted in exponential batch cultures, and was least impacted in stationary batch cultures. Although the amoA response was consistent with that of the sOUR, the amoA response was not as strong. The intracellular 16S rRNA/DNA ratio, as determined by fluorescence in situ hybridization, also did not uniformly correlate with the sOUR under conditions of inhibition or no inhibition. Finally, Cd(II)-mediated inhibition of N. europaea was attributed partially to oxidative stress.

  12. Abscisic acid (ABA) inhibits light-induced stomatal opening through calcium- and nitric oxide-mediated signaling pathways.

    PubMed

    Garcia-Mata, Carlos; Lamattina, Lorenzo

    2007-01-01

    Nitric oxide (NO) is an important signaling component of ABA-induced stomatal closure. However, only fragmentary data are available about NO effect on the inhibition of stomatal opening. Here, we present results supporting that, in Vicia faba guard cells, there is a critical Ca2+-dependent NO increase required for the ABA-mediated inhibition of stomatal opening. Light-induced stomatal opening was inhibited by exogenous NO in V. faba epidermal strips. Furthermore, ABA-mediated inhibition of stomatal opening was blocked by the specific NO scavenger cPTIO, supporting the involvement of endogenous NO in this process. Since the raise in Ca2+ concentration is a pre-requisite in ABA-mediated inhibition of stomatal opening, it was interesting to establish how does Ca2+, NO and ABA interact in the inhibition of light-induced stomatal opening. The permeable Ca2+ specific buffer BAPTA-AM blocked both ABA- and Ca2+- but not NO-mediated inhibition of stomatal opening. The NO synthase (NOS) specific inhibitor L-NAME prevented Ca2+-mediated inhibition of stomatal opening, indicating that a NOS-like activity was required for Ca2+ signaling. Furthermore, experiments using the NO specific fluorescent probe DAF-2DA indicated that Ca2+ induces an increase of endogenous NO. These results indicate that, in addition to the roles in ABA-triggered stomatal closure, both NO and Ca2+ are active components of signaling events acting in ABA inhibition of light-induced stomatal opening. Results also support that Ca2+ induces the NO production through the activation of a NOS-like activity.

  13. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Okon, E; Bursztyn, M

    1995-01-01

    Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 5% acetic acid. In several experiments, L-NAME 0.1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55%, colonic weight by 37%, and myeloperoxidase and NOS activity by 59% and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%, colonic weight by 21% and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two

  14. Cuprous oxide nanoparticles inhibit angiogenesis via down regulation of VEGFR2 expression

    NASA Astrophysics Data System (ADS)

    Song, Hongyuan; Wang, Wenbo; Zhao, Ping; Qi, Zhongtian; Zhao, Shihong

    2014-02-01

    Angiogenesis is a process that forms new blood capillaries from existing vessels, which is of great physiological and pathological significance. Although recent studies provide evidence that cuprous oxide nanoparticles (CO-NPs) may have biomedical potential, the mechanisms of CO-NPs in angiogenesis have not been investigated to date. We have studied the anti-angiogenic properties of CO-NPs on primary human umbilical vein endothelial cells (HUVECs). We found that CO-NPs were able to induce cell morphology changes and suppress cell proliferation, migration and tube formation in vitro and in vivo dose dependently. Furthermore, CO-NPs could induce cell apoptosis both at the early and late apoptotic stage and induce cell cycle arrest at S phase in a dose dependent manner. As signalling via the vascular endothelial growth factor receptor-2 (VEGFR2) is critical for angiogenic responses, we further explored the expression of VEGFR2 after the treatment of CO-NPs. They were found to inhibit VEGFR2 expression dose and time dependently both at the protein and mRNA level while had no effect on VEGF and VEGFR1 expression. Together, we report for the first time that CO-NPs can act as an anti-angiogenic agent by suppressing VEGFR2 expression, which may be a potential nanomedicine for angiogenesis therapy.Angiogenesis is a process that forms new blood capillaries from existing vessels, which is of great physiological and pathological significance. Although recent studies provide evidence that cuprous oxide nanoparticles (CO-NPs) may have biomedical potential, the mechanisms of CO-NPs in angiogenesis have not been investigated to date. We have studied the anti-angiogenic properties of CO-NPs on primary human umbilical vein endothelial cells (HUVECs). We found that CO-NPs were able to induce cell morphology changes and suppress cell proliferation, migration and tube formation in vitro and in vivo dose dependently. Furthermore, CO-NPs could induce cell apoptosis both at the early and

  15. ALDH2 attenuates Dox-induced cardiotoxicity by inhibiting cardiac apoptosis and oxidative stress.

    PubMed

    Gao, Yawen; Xu, Yan; Hua, Songwen; Zhou, Shenghua; Wang, Kangkai

    2015-01-01

    The anthracycline chemotherapy drug doxorubicin (DOX) is cardiotoxic. This study aimed to explore the effect of acetaldehyde dehydrogenase 2 (ALDH2), a detoxifying protein, on DOX-induced cardiotoxicity and unveil the underlying mechanisms. BALB/c mice were randomly divided in four groups: control group (no treatment), DOX group (DOX administration for myocardial damage induction), DOX + Daidzin group (DOX administration + Daidzin, an ALDH2 antagonist) and DOX + Alda-1 group (DOX administration + Alda-1, an ALDH2 agonist). Then, survival, haemodynamic parameters, expression of pro- and anti-apoptosis markers, reactive oxygen species (ROS) and 4-Hydroxynonenal (4-HNE) levels, expression and localization of NADPH oxidase 2 (NOX2) and its cytoplasmic subunit p47(PHOX), and ALDH2 expression and activity were assessed. Mortality rates of 0, 35, 5, and 70% were obtained in the control, DOX, DOX + Alda-1, and DOX + Daidzin groups, respectively, at the ninth weekend. Compared with control animals, DOX treatment resulted in significantly reduced left ventricular systolic pressure (LVSP) and ± dp/dt, and overtly increased left ventricular end-diastolic pressure (LVEDP); increased Bax expression and caspase-3/7 activity, and reduced Bcl-2 expression in the myocardium; increased ROS (about 2 fold) and 4-HNE adduct (3 fold) levels in the myocardium; increased NOX2 protein expression and membrane translocation of P47(PHOX). These effects were aggravated in the DOX + Daidzin group, DOX + Alda-1 treated animals showed partial or complete alleviation. Finally, Daidzin further reduced the DOX-repressed ALDH2 activity, which was partially rescued by Alda-1. These results indicated that ALDH2 attenuates DOX-induced cardiotoxicity by inhibiting oxidative stress, NOX2 expression and activity, and reducing myocardial apoptosis.

  16. Role of prostanoids and nitric oxide inhibition in rats with experimental hepatic fibrosis.

    PubMed

    Criado, M; Flores, O; Vázquez, M J; Esteller, A

    2000-09-01

    Nitric oxide (NO) and prostaglandins have been proposed as vasodilator substances involved in peripheral vasodilatation characteristic of the liver cirrhosis. A link between NO and prostanoids has been suggested. The present study investigated the effect of simultaneous blockade of both, NO synthase (NOS) and cyclooxigenase (COX) in sham-operated (SO), or rats with bile-duct ligation (BDL) in the development of liver fibrosis. Animals were distributed in two groups SO (n=15) or BDL (n=15). Treatments (5 days) started three weeks after surgical procedure. Both, SO and BDL animals were treated with indomethacin (INDO) (5 mg/kg/day) alone, with NG-nitro-L-arginine-methyl-ester (NAME) (4 mg/kg/day) alone or with INDO and NAME combination at the same doses. At the end of follow-up body weight, packed cell volume, mean arterial blood pressure (MAP) and heart rate were measured. Liver tissue was processed for histological studies. In this study, BDL animals showed a decreased MAP. Treatment with L-NAME in BDL rats increased MAP. The chronic COX inhibition alone did not play an important role in the haemodynamic changes. The BDL produced a loss of hepatic structure, with ductular metaplasia that occupied the greater part of the hepatic parenchyma. Also, an important degree of fibrosis was observed. Both NO and PG synthesis inhibitors, alone or in combination, induced enhancing collagen fiber deposition in the hepatic parenchyma. These findings support the notion that the interaction between the NOS and COX pathways should be relevant in hepatic cirrhosis in which both NOS and COX are induced.

  17. Iodine from bacterial iodide oxidization by Roseovarius spp. inhibits the growth of other bacteria.

    PubMed

    Zhao, Dan; Lim, Choon-Ping; Miyanaga, Kazuhiko; Tanji, Yasunori

    2013-03-01

    Microbial activities in brine, seawater, or estuarine mud are involved in iodine cycle. To investigate the effects of the microbiologically induced iodine on other bacteria in the environment, a total of 13 bacteria that potentially participated in the iodide-oxidizing process were isolated from water or biofilm at a location containing 131 μg ml(-1) iodide. Three distinct strains were further identified as Roseovarius spp. based on 16 S rRNA gene sequences after being distinguished by restriction fragment length polymorphism analysis. Morphological characteristics of these three Roseovarius spp. varied considerably across and within strains. Iodine production increased with Roseovarius spp. growth when cultured in Marine Broth with 200 μg ml(-1) iodide (I(-)). When 10(6) CFU/ml Escherichia coli, Pseudomonas aeruginosa, and Bacillus pumilus were exposed to various concentrations of molecular iodine (I(2)), the minimum inhibitory concentrations (MICs) were 0.5, 1.0, and 1.0 μg ml(-1), respectively. However, fivefold increases in the MICs for Roseovarius spp. were obtained. In co-cultured Roseovarius sp. IOB-7 and E. coli in Marine Broth containing iodide (I(-)), the molecular iodine concentration was estimated to be 0.76 μg ml(-1) after 24 h and less than 50 % of E. coli was viable compared to that co-cultured without iodide. The growth inhibition of E. coli was also observed in co-cultures with the two other Roseovarius spp. strains when the molecular iodine concentration was assumed to be 0.52 μg ml(-1).

  18. The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis

    PubMed Central

    Romano, B; Borrelli, F; Fasolino, I; Capasso, R; Piscitelli, F; Cascio, MG; Pertwee, RG; Coppola, D; Vassallo, L; Orlando, P; Di Marzo, V; Izzo, AA

    2013-01-01

    Background and Purpose The non-psychotropic cannabinoid cannabichromene is known to activate the transient receptor potential ankyrin-type1 (TRPA1) and to inhibit endocannabinoid inactivation, both of which are involved in inflammatory processes. We examined here the effects of this phytocannabinoid on peritoneal macrophages and its efficacy in an experimental model of colitis. Experimental Approach Murine peritoneal macrophages were activated in vitro by LPS. Nitrite levels were measured using a fluorescent assay; inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) and cannabinoid (CB1 and CB2) receptors were analysed by RT-PCR (and/or Western blot analysis); colitis was induced by dinitrobenzene sulphonic acid (DNBS). Endocannabinoid (anandamide and 2-arachidonoylglycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry. Colonic inflammation was assessed by evaluating the myeloperoxidase activity as well as by histology and immunohistochemistry. Key Results LPS caused a significant production of nitrites, associated to up-regulation of anandamide, iNOS, COX-2, CB1 receptors and down-regulation of CB2 receptors mRNA expression. Cannabichromene significantly reduced LPS-stimulated nitrite levels, and its effect was mimicked by cannabinoid receptor and TRPA1 agonists (carvacrol and cinnamaldehyde) and enhanced by CB1 receptor antagonists. LPS-induced anandamide, iNOS, COX-2 and cannabinoid receptor changes were not significantly modified by cannabichromene, which, however, increased oleoylethanolamide levels. In vivo, cannabichromene ameliorated DNBS-induced colonic inflammation, as revealed by histology, immunohistochemistry and myeloperoxidase activity. Conclusion and Implications Cannabichromene exerts anti-inflammatory actions in activated macrophages – with tonic CB1 cannabinoid signalling being negatively coupled to this effect – and ameliorates experimental murine colitis. PMID:23373571

  19. Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia

    NASA Technical Reports Server (NTRS)

    Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

    1999-01-01

    The aim of the present study was to determine whether inhibition of nitric oxide (NO) synthesis directly alters the tachycardia produced by sympathetically-derived norepinephrine. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 50 micromol/kg, i.v.), produced a marked rise in mean arterial blood pressure. This pressor response was associated with a fall in heart rate which involved the withdrawal of cardiac sympathetic nerve activity. The NO-donor, sodium nitroprusside (5 microg/kg, i.v.), produced a pronounced fall in mean arterial blood pressure but only a minor increase in heart rate. The beta-adrenoceptor agonist, isoproterenol (0.5 micromol/kg, i.v.), and the membrane-permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg, i.v.), produced falls in mean arterial blood pressure and pronounced increases in heart rate. The indirectly acting sympathomimetic agent, tyramine (0.5 mg/kg, i.v.), produced a pressor response and a tachycardia. The effects of sodium nitroprusside, tyramine, isoproterenol and 8-(4-chlorophenylthiol)-cAMP on mean arterial blood pressure were not markedly affected by L-NAME. However, the tachycardia produced by these agents was considerably exaggerated in the presence of this NO synthesis inhibitor. These findings suggest that L-NAME potentiates the tachycardia produced by sympathetically-derived norepinephrine. The increased responsiveness to norepinephrine may involve (i) a rapid up-regulation of cardiac beta1-adrenoceptors and cAMP signaling in cardiac pacemaker cells due to the loss of the inhibitory influence of cardiac NO, and (ii) the up-regulation of beta1-adrenoceptor-mediated signal transduction processes in response to the L-NAME-induced withdrawal of cardiac sympathetic nerve activity.

  20. A structural and dynamic investigation of the inhibition of catalase by nitric oxide.

    PubMed

    Candelaresi, Marco; Gumiero, Andrea; Adamczyk, Katrin; Robb, Kirsty; Bellota-Antón, César; Sangal, Vartul; Munnoch, John; Greetham, Gregory M; Towrie, Michael; Hoskisson, Paul A; Parker, Anthony W; Tucker, Nicholas P; Walsh, Martin A; Hunt, Neil T

    2013-11-28

    Determining the chemical and structural modifications occurring within a protein during fundamental processes such as ligand or substrate binding is essential to building up a complete picture of biological function. Currently, significant unanswered questions relate to the way in which protein structural dynamics fit within the structure-function relationship and to the functional role, if any, of bound water molecules in the active site. Addressing these questions requires a multidisciplinary approach and complementary experimental techniques that, in combination, enhance our understanding of the complexities of protein chemistry. We exemplify this philosophy by applying both physical and biological approaches to investigate the active site chemistry that contributes to the inhibition of the Corynebacterium glutamicum catalase enzyme by nitric oxide. Ultrafast two-dimensional infrared spectroscopy (2D-IR) experiments exploit the NO ligand as a local probe of the active site molecular environment and shows that catalase displays a dynamically-restricted, 'tight,' structure. X-ray crystallography studies of C. glutamicum catalase confirm the presence of a conserved chain of hydrogen-bonded bound water molecules that link the NO ligand and the protein scaffold. This combination of bound water and restricted dynamics stands in stark contrast to other haem proteins, such as myoglobin, that exhibit ligand transport functionality despite the presence of a similar distal architecture in close proximity to the ligand. We conclude not only that the bound water molecules in the catalase active site play an important role in molecular recognition of NO but also may be part of the mechanistic operation of this important enzyme.

  1. Effects of nitric oxide synthesis inhibition on mesenteric perfusion in young pigs.

    PubMed

    Alemany, C A; Oh, W; Stonestreet, B S

    1997-03-01

    We tested the hypothesis that nitric oxide (NO) modulates postprandial hyperemia in young pigs. To test this hypothesis, we studied five groups of 3-wk-old pigs: group 1: milk fed, N(G)-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) treated (n = 10); group 2: milk fed, placebo treated (n = 8); group 3: water fed, L-NMMA and L-Arg treated (n = 6); group 4: water fed, placebo treated (n = 4); and group 5: fasted sham fed, L-NMMA and L-Arg treated (n = 6). After catheter placement and electromagnetic flow probe instrumentation of the mesenteric artery, systemic blood pressure and mesenteric artery blood flow were measured during preprandial baseline, postprandial, and postprandial intra-arterial L-NMMA- and L-Arg-infused study periods. The same measurements were made in the milk- and water-fed placebo-treated groups except that diluent replaced the L-NMMA and L-Arg infusions. In the milk- and water-fed placebo-treated groups, a significant (analysis of variance, P < 0.05), postprandial hyperemia was observed. The change in blood flow was greater (P < 0.05) in the milk-fed group than in the water-fed group. Inhibition of NO synthesis with L-NMMA diminished (P < 0.05) the hyperemic responses to both water and milk feeding and resulted in a decrease (P < 0.05) in mesenteric artery perfusion in the fasted sham-fed state. We conclude that, in young pigs, NO is a modulator of mesenteric vascular tone in both the postprandial and fasted states.

  2. Prenylflavones from Psoralea corylifolia inhibit nitric oxide synthase expression through the inhibition of I-kappaB-alpha degradation in activated microglial cells.

    PubMed

    Lee, Ming Hong; Kim, Jae Yeon; Ryu, Jae-Ha

    2005-12-01

    The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) switches the function of NO from a physiological neuromodulator to a neurotoxic effector in central nervous system (CNS) after brain injury. From the methanol extracts of Psoralea corylifolia, we purified two inhibitors of NO production in lipopolysaccharide (LPS)-activated microglia by activity guided purification along with two inactive compounds. The active compounds were identified as a chromenoflavanone [7,8-dihydro-8-(4-hydroxyphenyl)-2,2-dimethyl-2H,6H-benzo-(1,2-b:5,4-b')dipyran-6-one] (1) and 4-hydroxylonchocarpin (2). And the inactive two compounds were identified as bavachinin (3) and bavachalcone (4) by spectral analysis. The compound 2 was isolated first time from this plant. Compounds 1 and 2 inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC(50)'s were 11.4, 10.2 microM, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at 10 muM as observed in Western blot analysis and RT-PCR experiment. Furthermore they inhibited the degradation of I-kappaB-alpha in activated microglia. These results imply that compounds 1 and 2 can be lead compounds for the development of neuroprotective drug with the inhibitory activity of NO overproduction by activated microglial cells.

  3. Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats.

    PubMed

    Czimmer, Jozsef; Király, Ágnes; Szabó, Imre Laszlo; Mózsik, Gyula; Sütő, Gabor

    2013-01-01

    Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50) dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.

  4. Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation.

    PubMed

    Roa-Espitia, Ana L; Hernández-Rendón, Eva R; Baltiérrez-Hoyos, Rafael; Muñoz-Gotera, Rafaela J; Cote-Vélez, Antonieta; Jiménez, Irma; González-Márquez, Humberto; Hernández-González, Enrique O

    2016-09-15

    Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca(2+) dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton.

  5. Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation

    PubMed Central

    Roa-Espitia, Ana L.; Hernández-Rendón, Eva R.; Baltiérrez-Hoyos, Rafael; Muñoz-Gotera, Rafaela J.; Cote-Vélez, Antonieta; Jiménez, Irma; González-Márquez, Humberto

    2016-01-01

    ABSTRACT Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton. PMID:27402964

  6. Oxidants downstream from superoxide inhibit nitric oxide production by vascular endothelium--a key role for selenium-dependent enzymes in vascular health.

    PubMed

    McCarty, M F

    1999-10-01

    Although superoxide can directly quench endothelium-generated nitric oxide (NO), there is considerable evidence that oxidants derived from superoxide--notably peroxides and their further derivatives--can also impair NO bioactivity. In part, this reflects inhibition of NO synthase activity, perhaps mediated by the oxidation of labile sulfhydryl groups, as well as the activation of protein kinase C. Selenium deficiency exacerbates these effects, presumably owing to the crucial role of selenium-dependent thioredoxin reductase and glutathione peroxidases in preventing and reversing oxidant damage to proteins. High-normal homocyst(e)ine levels may induce an 'effective selenium deficiency' by suppressing glutathione peroxidase transcription in endothelial cells. Considerable epidemiology, primarily of European origin, points to mediocre selenium nutrition as a significant vascular risk factor; the risk associated with elevated plasma homocyst(e)ine levels is now well established. In addition to preventing LDL oxidation, vitamin E can be expected to minimize the contribution of lipid peroxides to endothelial dysfunction. Lipoic acid, which can function in vivo as a versatile antioxidant and sulfhydryl reductant, may have particular value for protecting endothelium from oxidants; its clinical utility in diabetic neuropathy may reflect this benefit. Good selenium status, as well as supra-nutritional intakes of lipoic acid, may down-regulate cytokine-mediated endothelial activation by helping to maintain the proper structure of oxidant-labile proteins--such as tyrosine phosphatases--that modulate this signaling. It can be concluded that a number of supplemental nutrients--including selenium, vitamin E, lipoic acid, and the vitamins that promote catabolism of homocysteine--have the potential to promote vascular health by mitigating the adverse impact of superoxide-derived oxidants on endothelial function.

  7. Dopamine inhibits lipopolysaccharide-induced nitric oxide production through the formation of dopamine quinone in murine microglia BV-2 cells.

    PubMed

    Yoshioka, Yasuhiro; Sugino, Yuta; Tozawa, Azusa; Yamamuro, Akiko; Kasai, Atsushi; Ishimaru, Yuki; Maeda, Sadaaki

    2016-02-01

    Dopamine (DA) has been suggested to modulate functions of glial cells including microglial cells. To reveal the regulatory role of DA in microglial function, in the present study, we investigated the effect of DA on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine microglial cell line BV-2. Pretreatment with DA for 24 h concentration-dependently attenuated LPS-induced NO production in BV-2 cells. The inhibitory effect of DA on LPS-induced NO production was not inhibited by SCH-23390 and sulpiride, D1-like and D2-like DA receptor antagonists, respectively. In addition, pretreatment with (-)-(6aR,12bR)-4,6,6a,7,8,12b-Hexahydro-7-methylindolo[4,3-a]phenanthridin (CY 208-243) and bromocriptine, D1-like and D2-like DA receptor agonists, respectively, did not affect the LPS-induced NO production. N-Acetylcysteine, which inhibits DA oxidation, completely inhibited the effect of DA. Tyrosinase, which catalyzes the oxidation of DA to DA quionone (DAQ), accelerated the inhibitory effect of DA on LPS-induced NO production. These results suggest that DA attenuates LPS-induced NO production through the formation of DAQ in BV-2 cells.

  8. Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.

    PubMed

    Ivan, Ana L M; Campanini, Marcela Z; Martinez, Renata M; Ferreira, Vitor S; Steffen, Vinicius S; Vicentini, Fabiana T M C; Vilela, Fernanda M P; Martins, Frederico S; Zarpelon, Ana C; Cunha, Thiago M; Fonseca, Maria J V; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rúbia

    2014-09-05

    Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.

  9. Inhibition of nitric oxide synthase expression in activated microglia and peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.

    PubMed

    Lee, Ming Hong; Kim, Jae Yeon; Yoon, Jeong Hoon; Lim, Hyo Jin; Kim, Tae Hee; Jin, Changbae; Kwak, Wie-Jong; Han, Chang-Kyun; Ryu, Jae-Ha

    2006-09-01

    Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. A butanol fraction obtained from 50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at higher than 30 microg/mL as observed by western blot analysis and RT-PCR experiment. They also inhibited the degradation of I-kappaB-alpha in activated microglia. Moreover, they showed strong activity of peroxynitrite scavenging in a cell free bioassay system. These results imply that Opuntia ficus indica may have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

  10. Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system.

    PubMed

    Panich, Uraiwan; Tangsupa-a-nan, Vanida; Onkoksoong, Tasanee; Kongtaphan, Kamolratana; Kasetsinsombat, Kanda; Akarasereenont, Pravit; Wongkajornsilp, Adisak

    2011-05-01

    Ascorbic acid (AA) has been well known as a skin whitening agent, although attempts have been made to evaluate its protective role against ultraviolet (UV)-induced skin hyperpigmentation or increased melanin production. While melanogenesis is a defense mechanism of the skin against UV irradiation, melanin overproduction may also contribute to melanoma initiation. UVA might play a role in melanogenesis through promoting oxidative stress, which occurs as the result of increased formation of oxidants and/or reactive nitrogen species (RNS) including nitric oxide (NO). Therefore, we investigated the antimelanogenic effect of AA (7.5-120 μM) in association with its inhibitory effect on UVA-induced oxidant formation, NO production through endothelial and inducible NO synthases (eNOS and iNOS) activation and impairment of antioxidant defense using G361 human melanoma cells. Our study demonstrated a comparable ability of AA with that of kojic acid, a well-known tyrosinase inhibitor in inhibiting mushroom tyrosinase. Melanin content was reduced by AA, but neither tyrosinase activity nor mRNA levels were reduced by AA at non-cytotoxic concentrations in UVA-irradiated G361 cells. AA was shown to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA. We report herein that AA can protect against UVA-dependent melanogenesis possibly through the improvement of antioxidant defense capacity and inhibition of NO production through down-regulation of eNOS and iNOS mRNA.

  11. Fluoride-containing bioactive glasses inhibit pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human osteoblasts.

    PubMed

    Bergandi, Loredana; Aina, Valentina; Garetto, Stefano; Malavasi, Gianluca; Aldieri, Elisabetta; Laurenti, Enzo; Matera, Lina; Morterra, Claudio; Ghigo, Dario

    2010-02-12

    Bioactive glasses such as Hench's 45S5 (Bioglass) have applications to tissue engineering as well as bone repair, and the insertion of fluoride in their composition has been proposed to enhance their bioactivity. In view of a potential clinical application, we investigated whether fluoride-containing glasses exert toxic effects on human MG-63 osteoblasts, and whether and how fluoride, which is released in the cell culture medium, might play a role in such cytotoxicity. A 24h incubation with 50 microg/ml (12.5 microg/cm(2)) of fluoride-containing bioactive glasses termed HCaCaF(2) (F content: 5, 10 and 15 mol.%) caused the release of lactate dehydrogenase in the extracellular medium (index of cytotoxicity), the accumulation of intracellular malonyldialdehyde (index of lipoperoxidation), and the increase of glutathione consumption. Furthermore, fluoride-containing glasses inhibited the pentose phosphate oxidative pathway and the glucose 6-phosphate dehydrogenase activity. These effects are ascribable to the fluoride content/release of glass powders, since they were mimicked by NaF solutions and were prevented by dimethyl sulfoxide and tempol (two radical scavengers), by superoxide dismutase (a superoxide scavenger), and by glutathione (the most important intracellular antioxidant molecule), but not by apocynin (an inhibitor of NADPH oxidase). The presence of fluoride-containing glasses and NaF caused also the generation of reactive oxygen species, which was prevented by superoxide dismutase and catalase. The data suggest that fluoride released from glasses is the cause of MG-63 cell oxidative damage and is independent of NADPH oxidase activation. Our data provide a new mechanism to explain F(-) ions toxicity: fluoride could trigger, at least in part, an oxidative stress via inhibition of the pentose phosphate oxidative pathway and, in particular, through the oxidative inhibition of glucose 6-phosphate dehydrogenase.

  12. Inhibition of nerve stimulation-induced vasodilatation in corpora cavernosa of the pithed rat by blockade of nitric oxide synthase.

    PubMed Central

    Finberg, J. P.; Levy, S.; Vardi, Y.

    1993-01-01

    1. The effect of inhibition of nitric oxide synthase by NG-nitro-L-arginine methyl ester (L-NAME) on nerve stimulation-induced vasodilation in corpora cavernosa was studied in the pithed rat. Corporal vasodilation was estimated by the increase in ratio (corpora cavernosal pressure/systemic blood pressure; CP/BP) following electrical stimulation of the sacral part of the spinal cord. 2. L-NAME (2, 5, 10 and 25 mg kg-1) caused an increase in BP and a dose-dependent inhibition of the rise in the CP/BP ratio following stimulation. 3. The inhibitory effect of L-NAME (25 mg kg-1) on the corporal response to spinal cord stimulation, as well as the pressor response, was partially prevented by prior administration of L- but not D-arginine (400 mg kg-1, i.v.). 4. L-NAME (20 mg kg-1, i.v.) did not inhibit the rise in corporal pressure resulting from direct intracavernosal administration of papaverine (400 micrograms over 2 min). However, this response was inhibited by 5-hydroxytryptamine (20 micrograms kg-1, i.v.). 5. The results are indicative of a role of nitric oxide (NO) in the corporal vasodilator response to erectile stimulation. PMID:7683562

  13. Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20)

    PubMed Central

    Burrows, Natalie; Cane, Gaelle; Robson, Mathew; Gaude, Edoardo; J. Howat, William; Szlosarek, Peter W.; Pedley, R. Barbara; Frezza, Christian; Ashcroft, Margaret; Maxwell, Patrick H.

    2016-01-01

    The hypoxic tumour microenvironment represents an aggressive, therapy-resistant compartment. As arginine is required for specific hypoxia-induced processes, we hypothesised that arginine-deprivation therapy may be useful in targeting hypoxic cancer cells. We explored the effects of the arginine-degrading agent ADI-PEG20 on hypoxia-inducible factor (HIF) activation, the hypoxia-induced nitric oxide (NO) pathway and proliferation using HCT116 and UMUC3 cells and xenografts. The latter lack argininosuccinate synthetase (ASS1) making them auxotrophic for arginine. In HCT116 cells, ADI-PEG20 inhibited hypoxic-activation of HIF-1α and HIF-2α, leading to decreased inducible-nitric oxide synthase (iNOS), NO-production, and VEGF. Interestingly, combining hypoxia and ADI-PEG20 synergistically inhibited ASS1. ADI-PEG20 inhibited mTORC1 and activated the unfolded protein response providing a mechanism for inhibition of HIF and ASS1. ADI-PEG20 inhibited tumour growth, impaired hypoxia-associated NO-production, and decreased vascular perfusion. Expression of HIF-1α/HIF-2α/iNOS and VEGF were reduced, despite an increased hypoxic tumour fraction. Similar effects were observed in UMUC3 xenografts. In summary, ADI-PEG20 inhibits HIF-activated processes in two tumour models with widely different arginine biology. Thus, ADI-PEG20 may be useful in the clinic to target therapy-resistant hypoxic cells in ASS1-proficient tumours and ASS1-deficient tumours. PMID:26972697

  14. As(III) inhibits ultraviolet radiation-induced cyclobutane pyrimidine dimers repair via generation of nitric oxide in human keratinocytes

    PubMed Central

    Ding, Wei; Hudson, Laurie G.; Sun, Xi; Feng, Changjian; Liu, Ke Jian

    2008-01-01

    Inorganic arsenic enhances skin tumor formation when combined with other carcinogens including ultraviolet radiation (UVR). The inhibition of DNA damage repair by arsenic has been hypothesized to contribute to the co-carcinogenic activities of arsenic observed in vivo. Cyclobutane pyrimidine dimers (CPDs) are an important mutagenic UVR photoproduct and implicated in the genesis of non-melanoma skin cancer. The current study demonstrates that low concentrations of arsenite (As(III)) inhibit UVR-induced CPDs repair in a human keratinocyte cell line via nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Following As(III) treatment, NO production and iNOS expression are elevated. Little is known about regulation of iNOS by As(III) and further investigations indicated that p38 mitogen-activated protein kinase (p38 MAPK) and NF-κB are required for As(III) induction of iNOS expression. This As(III)-stimulated signaling cascade was involved in inhibition of UVR-induced CPDs repair as disruption of p38 MAPK activity and NF-κB nuclear translocation counteracted the effects of As(III) on CPD repair. Selective inhibition of iNOS ameliorated As(III) inhibition of CPDs repair thereby suggesting that iNOS is a downstream mediator of As(III) activity. These findings provide evidence that an As(III) stimulated signal transduction cascade culminating in elevated iNOS expression and NO generation is an underlying mechanism for inhibition of UVR-induced DNA damage repair by arsenic. PMID:18621123

  15. Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20).

    PubMed

    Burrows, Natalie; Cane, Gaelle; Robson, Mathew; Gaude, Edoardo; Howat, William J; Szlosarek, Peter W; Pedley, R Barbara; Frezza, Christian; Ashcroft, Margaret; Maxwell, Patrick H

    2016-03-14

    The hypoxic tumour microenvironment represents an aggressive, therapy-resistant compartment. As arginine is required for specific hypoxia-induced processes, we hypothesised that arginine-deprivation therapy may be useful in targeting hypoxic cancer cells. We explored the effects of the arginine-degrading agent ADI-PEG20 on hypoxia-inducible factor (HIF) activation, the hypoxia-induced nitric oxide (NO) pathway and proliferation using HCT116 and UMUC3 cells and xenografts. The latter lack argininosuccinate synthetase (ASS1) making them auxotrophic for arginine. In HCT116 cells, ADI-PEG20 inhibited hypoxic-activation of HIF-1α and HIF-2α, leading to decreased inducible-nitric oxide synthase (iNOS), NO-production, and VEGF. Interestingly, combining hypoxia and ADI-PEG20 synergistically inhibited ASS1. ADI-PEG20 inhibited mTORC1 and activated the unfolded protein response providing a mechanism for inhibition of HIF and ASS1. ADI-PEG20 inhibited tumour growth, impaired hypoxia-associated NO-production, and decreased vascular perfusion. Expression of HIF-1α/HIF-2α/iNOS and VEGF were reduced, despite an increased hypoxic tumour fraction. Similar effects were observed in UMUC3 xenografts. In summary, ADI-PEG20 inhibits HIF-activated processes in two tumour models with widely different arginine biology. Thus, ADI-PEG20 may be useful in the clinic to target therapy-resistant hypoxic cells in ASS1-proficient tumours and ASS1-deficient tumours.

  16. Quantum Capacitance in Topological Insulators

    PubMed Central

    Xiu, Faxian; Meyer, Nicholas; Kou, Xufeng; He, Liang; Lang, Murong; Wang, Yong; Yu, Xinxin; Fedorov, Alexei V.; Zou, Jin; Wang, Kang L.

    2012-01-01

    Topological insulators show unique properties resulting from massless, Dirac-like surface states that are protected by time-reversal symmetry. Theory predicts that the surface states exhibit a quantum spin Hall effect with counter-propagating electrons carrying opposite spins in the absence of an external magnetic field. However, to date, the revelation of these states through conventional transport measurements remains a significant challenge owing to the predominance of bulk carriers. Here, we report on an experimental observation of Shubnikov-de Haas oscillations in quantum capacitance measurements, which originate from topological helical states. Unlike the traditional transport approach, the quantum capacitance measurements are remarkably alleviated from bulk interference at high excitation frequencies, thus enabling a distinction between the surface and bulk. We also demonstrate easy access to the surface states at relatively high temperatures up to 60 K. Our approach may eventually facilitate an exciting exploration of exotic topological properties at room temperature. PMID:22993694

  17. N-acetyl-cysteine inhibits liver oxidative stress markers in BALB/c mice infected with Leishmania amazonensis

    PubMed Central

    Gasparotto, Juciano; Kunzler, Alice; Senger, Mario Roberto; de Souza, Celeste da Silva Freitas; de Simone, Salvatore Giovanni; Bortolin, Rafael Calixto; Somensi, Nauana; Dal-Pizzol, Felipe; Moreira, José Claudio Fonseca; Abreu-Silva, Ana Lúcia; Calabrese, Kátia da Silva; Silva, Floriano Paes; Gelain, Daniel Pens

    2017-01-01

    BACKGROUND Leishmaniasis is a parasitosis caused by several species of the genus Leishmania. These parasites present high resistance against oxidative stress generated by inflammatory cells. OBJECTIVES To investigate oxidative stress and molecular inflammatory markers in BALB/c mice infected with L. amazonensis and the effect of antioxidant treatment on these parameters. METHODS Four months after infection, oxidative and inflammatory parameters of liver, kidneys, spleen, heart and lungs from BALB/c mice were assessed. FINDINGS In liver, L. amazonensis caused thiol oxidation and nitrotyrosine formation; SOD activity and SOD2 protein content were increased while SOD1 protein content decreased. The content of the cytokines IL-1β, IL-6, TNF-α, and the receptor of advanced glycation endproducts (RAGE) increased in liver. Treatment with the antioxidant N-acetyl-cysteine (20 mg/kg b.w) for five days inhibited oxidative stress parameters. MAIN CONCLUSIONS L. amazonensis induces significant alterations in the redox status of liver but not in other organs. Acute antioxidant treatment alleviates oxidative stress in liver, but it had no effect on pro-inflammatory markers. These results indicate that the pathobiology of leishmaniasis is not restricted to the cutaneous manifestations and open perspectives for the development of new therapeutic approaches to the disease, especially for liver function. PMID:28177049

  18. Selective Irreversible Inhibition of Neuronal and Inducible Nitric-oxide Synthase in the Combined Presence of Hydrogen Sulfide and Nitric Oxide*

    PubMed Central

    Heine, Christian L.; Schmidt, Renate; Geckl, Kerstin; Schrammel, Astrid; Gesslbauer, Bernd; Schmidt, Kurt; Mayer, Bernd; Gorren, Antonius C. F.

    2015-01-01

    Citrulline formation by both human neuronal nitric-oxide synthase (nNOS) and mouse macrophage inducible NOS was inhibited by the hydrogen sulfide (H2S) donor Na2S with IC50 values of ∼2.4·10−5 and ∼7.9·10−5 m, respectively, whereas human endothelial NOS was hardly affected at all. Inhibition of nNOS was not affected by the concentrations of l-arginine (Arg), NADPH, FAD, FMN, tetrahydrobiopterin (BH4), and calmodulin, indicating that H2S does not interfere with substrate or cofactor binding. The IC50 decreased to ∼1.5·10−5 m at pH 6.0 and increased to ∼8.3·10−5 m at pH 8.0. Preincubation of concentrated nNOS with H2S under turnover conditions decreased activity after dilution by ∼70%, suggesting irreversible inhibition. However, when calmodulin was omitted during preincubation, activity was not affected, suggesting that irreversible inhibition requires both H2S and NO. Likewise, NADPH oxidation was inhibited with an IC50 of ∼1.9·10−5 m in the presence of Arg and BH4 but exhibited much higher IC50 values (∼1.0–6.1·10−4 m) when Arg and/or BH4 was omitted. Moreover, the relatively weak inhibition of nNOS by Na2S in the absence of Arg and/or BH4 was markedly potentiated by the NO donor 1-(hydroxy-NNO-azoxy)-l-proline, disodium salt (IC50 ∼ 1.3–2.0·10−5 m). These results suggest that nNOS and inducible NOS but not endothelial NOS are irreversibly inhibited by H2S/NO at modest concentrations of H2S in a reaction that may allow feedback inhibition of NO production under conditions of excessive NO/H2S formation. PMID:26296888

  19. Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats

    PubMed Central

    Fu, Chunlai; Dai, Xingui; Yang, You; Lin, Mengxiang; Cai, Yeping; Cai, Shaoxi

    2016-01-01

    Previous studies have identified that dexmedetomidine (DEX) treatment can ameliorate the acute lung injury (ALI) induced by lipopolysaccharide and ischemia-reperfusion. However, the molecular mechanisms by which DEX ameliorates lung injury remain unclear. The present study investigated whether DEX, which has been reported to exert effects on oxidative stress, mitochondrial permeability transition pores and apoptosis in other disease types, can exert protective effects in lipopolysaccharide (LPS)-induced ALI by inhibiting oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis. It was revealed that LPS-challenged rats exhibited significant lung injury, characterized by the deterioration of histopathology, vascular hyperpermeability, wet-to-dry weight ratio and oxygenation index (PaO2/FIO2), which was attenuated by DEX treatment. DEX treatment inhibited LPS-induced mitochondrial dysfunction, as evidenced by alleviating the cellular ATP and mitochondrial membrane potential in vitro. In addition, DEX treatment markedly prevented the LPS-induced mitochondrial-dependent apoptotic pathway in vitro (increases of cell apoptotic rate, cytosolic cytochrome c, and caspase 3 activity) and in vivo (increases of |terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells, cleaved caspase 3, Bax upregulation and Bcl-2 downregulation). Furthermore, DEX treatment markedly attenuated LPS-induced oxidative stress, as evidenced by downregulation of cellular reactive oxygen species in vitro and lipid peroxides in serum. Collectively, the present results demonstrated that DEX ameliorates LPS-induced ALI by reducing oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis. PMID:27959438

  20. Dexmedetomidine attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress, mitochondrial dysfunction and apoptosis in rats.

    PubMed

    Fu, Chunlai; Dai, Xingui; Yang, You; Lin, Mengxiang; Cai, Yeping; Cai, Shaoxi

    2017-01-01

    Previous studies have identified that dexmedetomidine (DEX) treatment can ameliorate the acute lung injury (ALI) induced by lipopolysaccharide and ischemia-reperfusion. However, the molecular mechanisms by which DEX ameliorates lung injury remain unclear. The present study investigated whether DEX, which has been reported to exert effects on oxidative stress, mitochondrial permeability transition pores and apoptosis in other disease types, can exert protective effects in lipopolysaccharide (LPS)‑induced ALI by inhibiting oxidative stress, mitochondrial dysfunction and mitochondrial‑dependent apoptosis. It was revealed that LPS‑challenged rats exhibited significant lung injury, characterized by the deterioration of histopathology, vascular hyperpermeability, wet‑to‑dry weight ratio and oxygenation index (PaO2/FIO2), which was attenuated by DEX treatment. DEX treatment inhibited LPS‑induced mitochondrial dysfunction, as evidenced by alleviating the cellular ATP and mitochondrial membrane potential in vitro. In addition, DEX treatment markedly prevented the LPS‑induced mitochondrial‑dependent apoptotic pathway in vitro (increases of cell apoptotic rate, cytosolic cytochrome c, and caspase 3 activity) and in vivo (increases of |terminal deoxynucleotidyl transferase dUTP nick‑end labeling positive cells, cleaved caspase 3, Bax upregulation and Bcl‑2 downregulation). Furthermore, DEX treatment markedly attenuated LPS‑induced oxidative stress, as evidenced by downregulation of cellular reactive oxygen species in vitro and lipid peroxides in serum. Collectively, the present results demonstrated that DEX ameliorates LPS‑induced ALI by reducing oxidative stress, mitochondrial dysfunction and mitochondrial-dependent apoptosis.

  1. Diaryl-1,2,4-oxadiazole antioxidants: synthesis and properties of inhibiting the oxidation of DNA and scavenging radicals.

    PubMed

    Zhao, Chao; Liu, Zai-Qun

    2013-04-01

    Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit (·)OH-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu(2+)/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+.)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant.

  2. Capacitive de-ionization electrode

    DOEpatents

    Daily, III, William D.

    2013-03-19

    An electrode "cell" for use in a capacitive deionization (CDI) reactor consists of the electrode support structure, a non-reactive conductive material, the electrode accompaniment or substrate and a flow through screen/separator. These "layers" are repeated and the electrodes are sealed together with gaskets between two end plates to create stacked sets of alternating anode and cathode electrodes in the CDI reactor.

  3. Inhibition of oxidative stress by low-molecular-weight polysaccharides with various functional groups in skin fibroblasts.

    PubMed

    Chen, Szu-Kai; Hsu, Chu-Hsi; Tsai, Min-Lang; Chen, Rong-Huei; Drummen, Gregor P C

    2013-09-25

    The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS' functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent.

  4. Cytochrome c upregulation during capacitation and spontaneous acrosome reaction determines the fate of pig sperm cells: linking proteome analysis.

    PubMed

    Choi, Yun-Jung; Uhm, Sang-Jun; Song, Sang-Jin; Song, Hyuk; Park, Jin-Ki; Kim, Teoan; Park, Chankyu; Kim, Jin-Hoi

    2008-02-01

    To identify the mechanisms underlying capacitation, we undertook a high-resolution differential proteomic analysis of pig sperm cells. Two-dimensional gel electrophoresis and subsequent MALDI-TOF mass spectrometry analyses led to identification of 56 differentially expressed proteins. After induction of capacitation in vitro, the well-established markers of the capacitation (lactadherin P47, acrosomal protein SP-10 precursor, prohibitin, proteasomes, DJ-1 protein and arylsulfatase-A) and TCA cycle proteins (isocitrate dehydrogenase, malate dehydrogenase and pyruvate dehydrogenase) were identified. During induction, cytochrome c expression via the p53 pathway increased, however apoptotic executors, such as caspase-3, decreased significantly. Therefore, we tested the hypothesis that cytochrome c upregulation in spermatozoa is capable of activating tyrosine phosphorylation for capacitation, rather than apoptosis. Exposure of sperm cells to soluble Na2CrO4 [Cr (VI)], which induces cytochrome c upregulation, caused a dose- and time-dependent increase in tyrosine phosphorylation of sperm proteins in non-capacitating medium. In contrast, supplementation of cyclosporin A, which blocks cytochrome c upregulation, inhibited tyrosine phosphorylation of sperm proteins. Furthermore, spermatozoa in capacitation medium or non-capacitation media supplemented with soluble Cr (VI) showed similar levels of capacitation. These findings indicate that differential expression of many of these proteins has previously been unrecognized in sperm cells incubated in capacitation medium also suggest that a gradual increase of cytochrome c during incubation to induce capacitation determines sperm cell fate, i.e., apoptosis or further development for fertilization.

  5. Inhibition of Estrogen-induced Growth of Breast Cancer by Targeting Mitochondrial Oxidants

    DTIC Science & Technology

    2009-04-01

    N- acetyl -L- cysteine ( NAC ), catalase, and the glutathione peroxidase mimic ebselen. mtTFA siRNA transfection inhibited estrogen-induced proliferation...chemical antioxidants, [N- acetylcysteine ( NAC ) and ebselen], inhibits estrogen induced expression of cell cycle genes as well as prevention of...8. The growth of E2-induced transformed clone was highly responsive to E2 and was inhibited by both antioxidants, ebselen and N- acetyl cysteine

  6. Waterproof, Ultrahigh Areal-Capacitance, Wearable Supercapacitor Fabrics.

    PubMed

    Yang, Yu; Huang, Qiyao; Niu, Liyong; Wang, Dongrui; Yan, Casey; She, Yiyi; Zheng, Zijian

    2017-02-24

    High-performance supercapacitors (SCs) are promising energy storage devices to meet the pressing demand for future wearable applications. Because the surface area of a human body is limited to 2 m(2) , the key challenge in this field is how to realize a high areal capacitance for SCs, while achieving rapid charging, good capacitive retention, flexibility, and waterproofing. To address this challenge, low-cost materials are used including multiwall carbon nanotube (MWCNT), reduced graphene oxide (RGO), and metallic textiles to fabricate composite fabric electrodes, in which MWCNT and RGO are alternatively vacuum-filtrated directly onto Ni-coated cotton fabrics. The composite fabric electrodes display typical electrical double layer capacitor behavior, and reach an ultrahigh areal capacitance up to 6.2 F cm(-2) at a high areal current density of 20 mA cm(-2) . All-solid-state fabric-type SC devices made with the composite fabric electrodes and water-repellent treatment can reach record-breaking performance of 2.7 F cm(-2) at 20 mA cm(-2) at the first charge-discharge cycle, 3.2 F cm(-2) after 10 000 charge-discharge cycles, zero capacitive decay after 10 000 bending tests, and 10 h continuous underwater operation. The SC devices are easy to assemble into tandem structures and integrate into garments by simple sewing.

  7. Parasitic capacitance characteristics of deep submicrometre grooved gate MOSFETs

    NASA Astrophysics Data System (ADS)

    Sreelal, S.; Lau, C. K.; Samudra, G. S.

    2002-03-01

    Grooved gate metal-oxide-semiconductor field-effect transistors (MOSFETs) are known to alleviate many of the short channel and hot carrier effects that arise when MOSFET devices are scaled down to very short channel lengths. However, they exhibit much higher parasitic capacitance with stronger bias dependence when compared to conventional planar devices. In this paper, we present a model for gate-to-drain and gate-to-source capacitance characteristics of a deep submicrometre grooved gate MOSFET. Both the intrinsic and extrinsic parts of the capacitance are modelled separately. In particular, the model presents a novel but simple way to account for the accumulation layer formation in the source/drain region of MOSFETs due to the application of the gate voltage. The results are compared with those obtained from a two-dimensional device simulator. The close match between the modelled and simulated data establishes the validity of the model. The model is then used to account for the superiority of capacitance characteristics of planar device structures and to arrive at optimization guidelines for grooved gate devices to match these characteristics.

  8. Wireless Charge Based Capacitance Measurement Circuits with On-Chip Spiral Inductor for Radio Frequency Identification Biosensor

    NASA Astrophysics Data System (ADS)

    Kim, Boram; Uno, Shigeyasu; Nakazato, Kazuo

    2012-04-01

    A wireless measuring system of charge based capacitance measurement (CBCM) circuit has been designed and demonstrated for biomedical applications. The radio frequency identification (RFID) chip that includes on-chip spiral inductor tag antenna, and RFID circuit, and CBCM sensor chip are fabricated within standard complementary metal oxide semiconductor (CMOS) process. The capacitance change caused by DNA detection can be converted into the voltage output using capacitance-to-voltage conversion circuit. To confirm the transmission of the capacitance, the poly-capacitor of fixed capacitance and on-chip spiral inductor tag antenna were fabricated using 1.2 µm, 2-metal, 2-poly CMOS technology. As a result of measurement, three different capacitances (34, 141, 564 fF) were detected wirelessly.

  9. Inhibition of Cholinesterases and Some Pro-Oxidant induced Oxidative Stress in Rats Brain by Two Tomato (Lycopersicon Esculentum) Varieties

    PubMed Central

    Oboh, G.; Bakare, O.O.; Ademosun, A.O.; Akinyemi, A.J.; Olasehinde, T.A.

    2015-01-01

    This study sought to investigate the effects of two tomato varieties [Lycopersicon esculentum Mill. var. esculentum (ESC) and Lycopersicon esculentum Mill. var. cerasiforme (CER)] on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in vitro. Phenolics content, carotenoids characterisation, inhibition of Fe2+ and quinolinic acid-induced malondialdehyde (MDA) production in rats brain homogenate and NO* scavenging abilities were also assesed in addition to the AChE and BChE inhibition assays. There was no significant difference in the AChE inhibitory ability of the samples, while CER had significantly higher BChE inhibitory activity. Furthermore, the tomatoes inhibited Fe2+ and quinolinic acid-induced MDA production and further exhibited antioxidant activities through their NO* scavenging abilities. There was no significant difference in the phenolic content of the samples, while significantly high amounts of lycopene were detected in the tomatoes. The cholinesterase-inhibition and antioxidant properties of the “tomatoes” could make them good dietary means for the management of neurodegenerative disorders.

  10. The calcium channel blocker verapamil inhibits oxidative stress response in Candida albicans.

    PubMed

    Yu, Qilin; Xiao, Chenpeng; Zhang, Kailun; Jia, Chang; Ding, Xiaohui; Zhang, Bing; Wang, Yu; Li, Mingchun

    2014-04-01

    Candida albicans is a common opportunistic fungal pathogen, causing both superficial candidiasis and life-threatening systemic infections in immune-compromised individuals. Calcium signaling is responsible for this pathogen in responding to several stresses, such as antifungal drugs, alkaline pH and membrane-perturbing agents. Our recent study revealed that it is also involved in oxidative stress response. In this study, we investigated the effect of verapamil, an L-type voltage-gated calcium channel blocker, on oxidative stress response in this fungus. The addition of verapamil resulted in increased sensitivity to the oxidative agent H2O2, which is associated with a decrease of calcium fluctuation under the stress. Moreover, this agent caused enhanced oxidative stress, with increased levels of ROS and enhanced dysfunction of the mitochondria under the oxidative stress. Further investigations in SOD activity, GSH contents and expression of oxidative stress response-related genes indicated that the effect of verapamil is related to the repression of oxidative stress response. Our findings demonstrated that verapamil has an inhibitory effect on oxidative stress response, confirming the relationship between calcium signaling and oxidative stress in C. albicans. Therefore, calcium channels may be potential targets for therapy to enhance the efficacy of oxidative stress against C. albicans-related infections.

  11. Growth of ammonia-oxidizing archaea in soil microcosms is inhibited by acetylene.

    PubMed

    Offre, Pierre; Prosser, James I; Nicol, Graeme W

    2009-10-01

    Autotrophic ammonia-oxidizing bacteria were considered to be responsible for the majority of ammonia oxidation in soil until the recent discovery of the autotrophic ammonia-oxidizing archaea. To assess the relative contributions of bacterial and archaeal ammonia oxidizers to soil ammonia oxidation, their growth was analysed during active nitrification in soil microcosms incubated for 30 days at 30 degrees C, and the effect of an inhibitor of ammonia oxidation (acetylene) on their growth and soil nitrification kinetics was determined. Denaturing gradient gel electrophoresis (DGGE) analysis of bacterial ammonia oxidizer 16S rRNA genes did not detect any change in their community composition during incubation, and quantitative PCR (qPCR) analysis of bacterial amoA genes indicated a small decrease in abundance in control and acetylene-containing microcosms. DGGE fingerprints of archaeal amoA and 16S rRNA genes demonstrated changes in the relative abundance of specific crenarchaeal phylotypes during active nitrification. Growth was also indicated by increases in crenarchaeal amoA gene copy number, determined by qPCR. In microcosms containing acetylene, nitrification and growth of the crenarchaeal phylotypes were suppressed, suggesting that these crenarchaea are ammonia oxidizers. Growth of only archaeal but not bacterial ammonia oxidizers occurred in microcosms with active nitrification, indicating that ammonia oxidation was mostly due to archaea in the conditions of the present study.

  12. Hydrogen-rich water alleviates aluminum-induced inhibition of root elongation in alfalfa via decreasing nitric oxide production.

    PubMed

    Chen, Meng; Cui, Weiti; Zhu, Kaikai; Xie, Yanjie; Zhang, Chunhua; Shen, Wenbiao

    2014-02-28

    One of the earliest and distinct symptoms of aluminum (Al) toxicity is the inhibition of root elongation. Although hydrogen gas (H2) is recently described as an important bio-regulator in plants, whether and how H2 regulates Al-induced inhibition of root elongation is largely unknown. To address these gaps, hydrogen-rich water (HRW) was used to investigate a physiological role of H2 and its possible molecular mechanism. Individual or simultaneous (in particular) exposure of alfalfa seedlings to Al, or a fresh but not old nitric oxide (NO)-releasing compound sodium nitroprusside (SNP), not only increased NO production, but also led to a significant inhibition of root elongation. Above responses were differentially alleviated by pretreatment with 50% saturation of HRW. The addition of HRW also alleviated the appearance of Al toxicity symptoms, including the improvement of seedling growth and less accumulation of Al. Subsequent results revealed that the removal of NO by the NO scavenger, similar to HRW, could decrease NO production and alleviate Al- or SNP-induced inhibition of root growth. Thus, we proposed that HRW alleviated Al-induced inhibition of alfalfa root elongation by decreasing NO production. Such findings may be applicable to enhance crop yield and improve stress tolerance.

  13. Role of nitric oxide synthase inhibition in the acute hypertensive response to intracerebroventricular cadmium

    PubMed Central

    Demontis, Maria Piera; Varoni, Maria Vittoria; Volpe, Anna Rita; Emanueli, Costanza; Madeddu, Paolo

    1998-01-01

    In the rat, intracerebroventricular (i.c.v.) injection of cadmium, a pollutant with long biological half-life, causes a sustained increase in blood pressure at doses that are ineffective by peripheral route. Since cadmium inhibits calcium-calmodulin constitutive nitric oxide (NO) synthase in cytosolic preparations of rat brain, this mechanism may be responsible for the acute pressor action of this heavy metal.To test this possibility, we evaluated the effect of i.c.v. injection of 88 nmol cadmium in normotensive unanaesthetized Wistar rats, which were i.c.v. pre-treated with: (1) saline (control), (2) L-arginine (L-Arg), to increase the availability of substrate for NO biosynthesis, (3) D-arginine (D-Arg), (4) 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1), an NO donor, or (5) CaCl2, a cofactor of brain calcium-calmodulin-dependent cNOSI. In additional experiments, the levels of L-citrulline (the stable equimolar product derived from enzymatic cleavage of L-Arg by NO synthase) were determined in the brain of vehicle- or cadmium-treated rats.The pressor response to cadmium reached its nadir at 5 min (43±4 mmHg) and lasted over 20 min in controls. L-Citrulline/protein content was reduced from 35 up to 50% in the cerebral cortex, pons, hippocampus, striatus, hypothalamus (P<0.01) of cadmium-treated rats compared with controls. Central injection of NG nitro-L-arginine-methylester (L-NAME) also reduced the levels of L-citrulline in the brain.Both the magnitude and duration of the response were attenuated by 1.21 and 2.42 μmol SIN-1 (32±3 and 15±4 mmHg, P<0.05), or 1 μmol CaCl2 (6±4 mmHg, P<0.05). Selectivity of action exerted by SIN-1 was confirmed by the use of another NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). Both L-Arg and D-Arg caused a mild but significant attenuation in the main phase of the pressor response evoked by cadmium. However, only L-Arg reduced the magnitude of the delayed, pressor response. Despite their similarity in

  14. Chronic PARP-1 inhibition reduces carotid vessel remodeling and oxidative damage of the dorsal hippocampus in spontaneously hypertensive rats

    PubMed Central

    Eros, Krisztian; Magyar, Klara; Deres, Laszlo; Skazel, Arpad; Riba, Adam; Vamos, Zoltan; Kalai, Tamas; Gallyas, Ferenc; Sumegi, Balazs; Toth, Kalman

    2017-01-01

    Vascular remodeling during chronic hypertension may impair the supply of tissues with oxygen, glucose and other compounds, potentially unleashing deleterious effects. In this study, we used Spontaneously Hypertensive Rats and normotensive Wistar-Kyoto rats with or without pharmacological inhibition of poly(ADP-ribose)polymerase-1 by an experimental compound L-2286, to evaluate carotid artery remodeling and consequent damage of neuronal tissue during hypertension. We observed elevated oxidative stress and profound thickening of the vascular wall with fibrotic tissue accumulation induced by elevated blood pressure. 32 weeks of L-2286 treatment attenuated these processes by modulating mitogen activated protein kinase phosphatase-1 cellular levels in carotid arteries. In hypertensive animals, vascular inflammation and endothelial dysfunction was observed by NF-κB nuclear accumulation and impaired vasodilation to acetylcholine, respectively. Pharmacological poly(ADP-ribose)polymerase-1 inhibition interfered in these processes and mitigated Apoptosis Inducing Factor dependent cell death events, thus improved structural and functional alterations of carotid arteries, without affecting blood pressure. Chronic poly(ADP-ribose)polymerase-1 inhibition protected neuronal tissue against oxidative damage, assessed by nitrotyrosine, 4-hydroxinonenal and 8-oxoguanosine immunohistochemistry in the area of Cornu ammonis 1 of the dorsal hippocampus in hypertensive rats. In this area, extensive pyramidal cell loss was also attenuated by treatment with lowered poly(ADP-ribose)polymer formation. It also preserved the structure of fissural arteries and attenuated perivascular white matter lesions and reactive astrogliosis in hypertensive rats. These data support the premise in which chronic poly(ADP-ribose)polymerase-1 inhibition has beneficial effects on hypertension related tissue damage both in vascular tissue and in the hippocampus by altering signaling events, reducing oxidative

  15. Structural Basis for Isoform-Selective Inhibition in Nitric Oxide Synthase

    PubMed Central

    LI, HUIYING

    2013-01-01

    CONSPECTUS Nitric oxide synthase (NOS) converts L-arginine into L-citrulline and releases the important signaling molecule nitric oxide (NO). In the cardiovascular system NO produced by endothelial NOS (eNOS) relaxes smooth muscle which controls vascular tone and blood pressure.Neuronal NOS (nNOS) produces NO in the brain, where it influences a variety of neural functions such as neural transmitter release. NO can also support immune system, serving as a cytotoxic agent during infections. Even with all of these important functions, NO is a free radical, and, when overproduced, it can cause tissue damage. This mechanism can operate in many neurodegenerative diseases, and as a result, the development of drugs targeting nNOS is a desirable therapeutic goal. However, the active sites of all 3 human isoforms are very similar, and designing inhibitors specific for nNOS is a challenging problem. It is critically important, for example, not to inhibit eNOS owing to its central role in controlling blood pressure. In this Account we summarize our efforts in collaboration with Rick Silverman at Northwestern University to develop drug candidates that specifically target NOS using crystallography, computational chemistry, and organic synthesis. As a result we have developed aminopyridine compounds that are 3,800 fold more selective for nNOS than eNOS, some of which show excellent neuro-protective effects in animal models. Our group has solved approximately 130 NOS-inhibitor crystal structures which have provided the structural basis for our design efforts. Initial crystal structures of nNOS and eNOS bound to selective dipeptide inhibitors showed that a single amino acid difference (Asp in nNOS and Asn in eNOS) results in much tighter binding to nNOS. The NOS active site is open and rigid, which produces few large structural changes when inhibitors bind. However, we have found that relatively small changes in the active site and inhibitor chirality can account for large

  16. New strategy to rescue the inhibition of osteogenesis of human bone marrow-derived mesenchymal stem cells under oxidative stress: combination of vitamin C and graphene foams

    PubMed Central

    Wang, Feng; Lu, Ye; Yin, Peipei; Jiang, Chaolai; Liu, Yingjie; Li, Hua; Yu, Xiaowei; Sun, Yuqiang

    2016-01-01

    To rescue the oxidative stress induced inhibition of osteogenesis, vitamin C (VC) was chemically modified onto three-dimensional graphene foams (3D GFs), then their regulation on osteogenesis of human bone marrow-derived mesenchymal stem cells (BM-MSCs) was studied. Combined action of VC + GF significantly decreased H2O2-induced oxidative stress, and rescued H2O2-inhibited cell viability, differentiation and osteogenesis of BM-MSCs in vitro. Further studies revealed that Wnt pathway may be involved in this protection of osteogenesis. Furthermore, an in vivo mouse model of BM-MSCs transplantation showed that VC + GF remarkably rescued oxidative stress inhibited calcium content and bone formation. The combination of VC and GF exhibited more pronounced protective effects against oxidative stress induced inhibition of osteogenesis, compared to monotherapy of VC or GF. Our study proposed a new strategy in stem cell-based therapies for treating bone diseases. PMID:27713129

  17. Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies.

    PubMed

    Hossain, Fokhrul; Al-Khami, Amir A; Wyczechowska, Dorota; Hernandez, Claudia; Zheng, Liqin; Reiss, Krzystoff; Valle, Luis Del; Trillo-Tinoco, Jimena; Maj, Tomasz; Zou, Weiping; Rodriguez, Paulo C; Ochoa, Augusto C

    2015-11-01

    Myeloid-derived suppressor cells (MDSC) promote tumor growth by inhibiting T-cell immunity and promoting malignant cell proliferation and migration. The therapeutic potential of blocking MDSC in tumors has been limited by their heterogeneity, plasticity, and resistance to various chemotherapy agents. Recent studies have highlighted the role of energy metabolic pathways in the differentiation and function of immune cells; however, the metabolic characteristics regulating MDSC remain unclear. We aimed to determine the energy metabolic pathway(s) used by MDSC, establish its impact on their immunosuppressive function, and test whether its inhibition blocks MDSC and enhances antitumor therapies. Using several murine tumor models, we found that tumor-infiltrating MDSC (T-MDSC) increased fatty acid uptake and activated fatty acid oxidation (FAO). This was accompanied by an increased mitochondrial mass, upregulation of key FAO enzymes, and increased oxygen consumption rate. Pharmacologic inhibition of FAO blocked immune inhibitory pathways and functions in T-MDSC and decreased their production of inhibitory cytokines. FAO inhibition alone significantly delayed tumor growth in a T-cell-dependent manner and enhanced the antitumor effect of adoptive T-cell therapy. Furthermore, FAO inhibition combined with low-dose chemotherapy completely inhibited T-MDSC immunosuppressive effects and induced a significant antitumor effect. Interestingly, a similar increase in fatty acid uptake and expression of FAO-related enzymes was found in human MDSC in peripheral blood and tumors. These results support the possibility of testing FAO inhibition as a novel approach to block MDSC and enhance various cancer therapies.

  18. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages.

    PubMed

    Pahan, K; Sheikh, F G; Namboodiri, A M; Singh, I

    1997-12-01

    This study explores the role of mevalonate inhibitors in the activation of NF-kbeta and the induction of inducible nitric oxide synthase (iNOS) and cytokines (TNF-alpha, IL-1beta, and IL-6) in rat primary astrocytes, microglia, and macrophages. Lovastatin and sodium phenylacetate (NaPA) were found to inhibit LPS- and cytokine-mediated production of NO and expression of iNOS in rat primary astrocytes; this inhibition was not due to depletion of end products of mevalonate pathway (e.g., cholesterol and ubiquinone). Reversal of the inhibitory effect of lovastatin on LPS-induced iNOS expression by mevalonate and farnesyl pyrophosphate and reversal of the inhibitory effect of NaPA on LPS-induced iNOS expression by farnesyl pyrophosphate, however, suggests a role of farnesylation in the LPS-mediated induction of iNOS. The inhibition of LPS-mediated induction of iNOS by FPT inhibitor II, an inhibitor of Ras farnesyl protein transferase, suggests that farnesylation of p21(ras) or other proteins regulates the induction of iNOS. Inhibition of LPS-mediated activation of NF-kbeta by lovastatin, NaPA, and FPT inhibitor II in astrocytes indicates that the observed inhibition of iNOS expression is mediated via inhibition of NF-kbeta activation. In addition to iNOS, lovastatin and NaPA also inhibited LPS-induced expression of TNF-alpha, IL-1beta, and IL-6 in rat primary astrocytes, microglia, and macrophages. This study delineates a novel role of the mevalonate pathway in controlling the expression of iNOS and different cytokines in rat astrocytes, microglia, and macrophages that may be important in developing therapeutics against cytokine- and NO-mediated neurodegenerative diseases.

  19. The involvement of nitric oxide in ultraviolet-B-inhibited pollen germination and tube growth of Paulownia tomentosa in vitro.

    PubMed

    He, Jun-Min; Bai, Xiao-Ling; Wang, Rui-Bin; Cao, Bing; She, Xiao-Ping

    2007-10-01

    The role of nitric oxide (NO) in the ultraviolet-B radiation (UV-B)-induced reduction of in vitro pollen germination and tube growth of Paulownia tomentosa Steud. was studied. Results showed that exposure of the pollen to 0.4 and 0.8 W m(-2) UV-B radiation for 2 h resulted in not only the reduction of pollen germination and tube growth but also the enhancement of NO synthase (NOS, EC 1.14.13.39) activity and NO production in pollen grain and tube. Also, exogenous NO donors sodium nitroprusside and S-nitrosoglutathione inhibited both pollen germination and tube growth in a dose-dependence manner. NOS inhibitor N(G)-nitro-l-Arg-methyl eater (l-NAME) and NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) not only largely prevented the NO generation but also partly reversed the UV-B-inhibited pollen germination and tube growth. These results indicate that UV-B radiation inhibits pollen germination and tube growth partly via promoting NO production in pollen grain and tube by a NOS-like enzyme. Additionally, a guanylyl cyclase inhibitor 6-anilino-5,8-quinolinequinone (LY-83583) prevented both the UV-B- and NO donors-inhibited pollen germination and tube growth, suggesting that the NO function is mediated by cyclic guanosine 5'-monophosphate. However, the effects of c-PTIO, l-NAME and LY-83583 on the UV-B-inhibited pollen germination and tube growth were only partial, suggesting that there are NO-independent pathways in UV-B signal networks.

  20. A new diffusion-inhibited oxidation-resistant coating for superalloys

    NASA Technical Reports Server (NTRS)

    Gedwill, M. A.; Glasgow, T. K.; Levine, S. R.

    1981-01-01

    A concept for enhanced protection of superalloys consists of adding an oxidation- and diffusion-resistant cermet layer between the superalloy and the outer oxidation-resistant metallic alloy coating. Such a duplex coating was compared with a physical-vapor-deposited (PVD) NiCrAlY coating in cyclic oxidation at 1150 C. The substrate alloy was MA 754 - an oxide-dispersion-strengthened superalloy that is difficult to coat. The duplex coating, applied by plasma spraying, outperformed the PVD coating on the basis of weight change and both macroscopic and metallographic observations.

  1. Rocuronium Bromide Inhibits Inflammation and Pain by Suppressing Nitric Oxide Production and Enhancing Prostaglandin E2 Synthesis in Endothelial Cells

    PubMed Central

    2016-01-01

    Purpose Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells. Methods For this study, calf pulmonary artery endothelial (CPAE) cells were used, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, nitric oxide detection, and prostaglandin E2 immunoassay were conducted. Results Rocuronium bromide treatment inhibited endothelial nitric oxide synthase and suppressed nitric oxide production in CPAE cells. Rocuronium bromide activated cyclooxygenase-2, inducible nitric oxide synthase and increased prostaglandin E2 synthesis in CPAE cells. Conclusions Rocuronium bromide induced inflammation and pain in CPAE cells. Suppressing nitric oxide production and enhancing prostaglandin E2 synthesis might be associated with rocuronium bromide-induced injection pain or withdrawal movement. PMID:28043117

  2. Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress.

    PubMed

    Qiang, Xiaoyan; Xu, Lulu; Zhang, Miao; Zhang, Pengcheng; Wang, Yinhang; Wang, Yongchen; Zhao, Zheng; Chen, Huan; Liu, Xie; Zhang, Yubin

    2016-04-15

    Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid β-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation.

  3. Radiofrequency Renal Denervation Protects the Ischemic Heart via Inhibition of GRK2 and Increased Nitric Oxide Signaling

    PubMed Central

    Polhemus, David J.; Gao, Juan; Scarborough, Amy L.; Trivedi, Rishi; McDonough, Kathleen H.; Goodchild, Traci T.; Smart, Frank

    2016-01-01

    Rationale: Catheter-based renal denervation (RDN) is currently under development for the treatment of resistant hypertension and is thought to reduce blood pressure via interruption of sympathetic pathways that modulate cardiovascular function. The sympathetic nervous system also plays a critical role in the pathogenesis of acute myocardial infarction and heart failure. Objective: We examined whether treatment with radiofrequency (RF)-RDN would protect the heart against subsequent myocardial ischemia/reperfusion injury via direct effects on the myocardium. Methods and Results: Spontaneously hypertensive rats received either bilateral RF-RDN or sham-RDN. At 4 weeks after RF-RDN (n=14) or sham-RDN (n=14) treatment, spontaneously hypertensive rats were subjected to 30 minutes of transient coronary artery occlusion and 24 hours –7 days reperfusion. Four weeks after RF-RDN, myocardial oxidative stress was markedly attenuated, and transcription and translation of antioxidants, superoxide dismutase 1 and glutathione peroxidase-1, were significantly upregulated compared with sham-RDN spontaneously hypertensive rats. RF-RDN also inhibited myocardial G protein–coupled receptor kinase 2 pathological signaling and enhanced myocardial endothelial nitric oxide synthase function and nitric oxide signaling. RF-RDN therapy resulted in a significant reduction in myocardial infarct size per area at risk compared with sham-RDN (26.8 versus 43.9%; P<0.01) at 24 hours postreperfusion and significantly improved left ventricular function at 7 days after myocardial ischemia/reperfusion. Conclusions: RF-RDN reduced oxidative stress, inhibited G protein–coupled receptor kinase 2 signaling, increased nitric oxide bioavailability, and ameliorated myocardial reperfusion injury in the setting of severe hypertension. These findings provide new insights into the remote cardioprotective effects of RF-RDN acting directly on cardiac myocytes to attenuate cell death and protect against ischemic

  4. Regulation of Sperm Capacitation and the Acrosome Reaction by PIP 2 and Actin Modulation.

    PubMed

    Breitbart, Haim; Finkelstein, Maya

    2015-01-01

    Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP 2 ) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP 2 is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP 2 to the cells. Reduction of PIP 2 synthesis inhibits actin polymerization and motility, while increasing PIP 2 synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP 2 and F-actin. During capacitation there was an increase in PIP 2 and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP 2 . Stimulation of phospholipase C, by Ca 2 + -ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP 2 and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.

  5. Regulation of sperm capacitation and the acrosome reaction by PIP2 and actin modulation

    PubMed Central

    Breitbart, Haim; Finkelstein, Maya

    2015-01-01

    Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP2) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP2 is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP2 to the cells. Reduction of PIP2 synthesis inhibits actin polymerization and motility, while increasing PIP2 synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP2 and F-actin. During capacitation there was an increase in PIP2 and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP2. Stimulation of phospholipase C, by Ca2+-ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP2 and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility. PMID:25966627

  6. Benidipine, a dihydropyridine-calcium channel blocker, inhibits lysophosphatidylcholine-induced endothelial injury via stimulation of nitric oxide release.

    PubMed

    Matsubara, Masahiro; Yao, Kozo; Hasegawa, Kazuhide

    2006-01-01

    Benidipine hydrochloride (benidipine), which is a long-lasting dihydropyridine calcium channel blocker, exerts antihypertensive action via inhibition of Ca(2+) influx through L-type voltage-dependent calcium channels. In addition, benidipine is shown to restore endothelial function. However, the mechanisms whereby benidipine has protective effects on endothelium are poorly defined. Nitric oxide (NO), which is produced by endothelial NO synthase (eNOS), plays important roles in endothelial function. In this study, we examined effects of benidipine on NO production from human umbilical vein endothelial cells. Benidipine (0.3-10 microM) augmented eNOS expression and total eNOS enzymatic activities. Benidipine also promoted the production of NO and the accumulation of cGMP, a second messenger of NO. Lysophosphatidylcholine (lysoPC), a component of oxidized low-density lipoproteins, induced caspase-3 activation followed by apoptosis of endothelial cells. Benidipine (0.3-10 microM) prevented lysoPC-induced caspase-3 activation, which was canceled by Nomega-nitro-L-arginine-methyl ester (L-NAME) (250-2500 microM), an inhibitor of NOS. Moreover, diethylenetetraamine NONOate (30-100 microM), a NO donor, inhibited the caspase-3 activation. These results suggested that the increase in NO production by benidipine might be involved in the inhibition of caspase induction. The direct enhancement of endothelial NO release by benidipine may be in part responsible for amelioration of endothelial dysfunction.

  7. Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage.

    PubMed

    Song, Meijun; Wu, Hongcheng; Wu, Shibo; Ge, Ting; Wang, Guoan; Zhou, Yingyan; Sheng, Shimo; Jiang, Jingbo

    2016-12-01

    Lung cancer is the leading cause of cancer death worldwide and its clinical management remains challenge. Here, we repurposed antibiotic levofloxacin for lung cancer treatment. We show that levofloxacin is effectively against a panel of lung cancer cell lines via inhibiting proliferation and inducing apoptosis, regardless of cellular origin and genetic pattern, in in vitro cell culture system and in vivo xenograft lung tumor model. Mechanistically, levofloxacin inhibits activities of mitochondrial electron transport chain complex I and III, leading to inhibition of mitochondrial respiration and reduction of ATP production. In addition, levofloxacin significantly increases levels of ROS, mitochondrial superoxide and hydrogen peroxide in vitro and oxidative stress markers (HEL and 4-HNE) in vivo. Antioxidants, such as NAC and vitamin C, prevent the inhibitory effects of levofloxacin, confirming the induction of oxidative damage as the mechanism of its action in lung cancer cells. Our work demonstrates that levofloxacin is a useful addition to the treatment of lung cancer. Our work also suggests that targeting mitochondria may be an alternative therapeutic strategy for lung cancer treatment.

  8. D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects.

    PubMed

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Yorita, K; Chung, S P; Tran, D H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-10-01

    Angiogenesis is critical for cancer growth and metastasis. Steps of angiogenesis are energy consuming, while vascular endothelial cells are highly glycolytic. Glioblastoma multiforme (GBM) is a highly vascular tumor and this enhances its aggressiveness. D-amino acid oxidase (DAO) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates. Oxidative stress-energy depletion (OSED) therapy was recently reported (El Sayed et al., Cancer Gene Ther, 19, 1-18, 2012). OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate (3BP), a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate (El Sayed et al., J Bioenerg Biomembr, 44, 61-79, 2012). Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase. Here, we report that DAO, 3BP and citrate significantly inhibited angiogenesis, decreased the number of vascular branching points and shortened the length of vascular tubules. OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar. Human GBM cells (U373MG) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside, while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells.

  9. delta-Aminolevulinate dehydratase inhibition by ascorbic acid is mediated by an oxidation system existing in the hepatic supernatant.

    PubMed

    Beber, F A; Wollmeister, J; Brigo, M J; Silva, M C; Pereira, C N; Rocha, J B

    1998-01-01

    The effect of ascorbic acid (AA) on hepatic delta-aminolevulinic acid dehydratase (ALA-D) activity was studied. AA decreased enzyme activity by reducing maximum velocity and tended to increase the Michaelis constant. ALA-D inactivation by AA occurred similarly both in air and argonium atmosphere incubation. DTT reduced considerably the inhibitory effect of AA on ALA-D, but glutathione was ineffective in reversing inact