Mitochondrial dysfunction leads to NOX activation: A novel mechanism to maintain high glycolysis in cancer cells

Increased glycolysis and oxidative stress are common features of cancer cells. These metabolic alterations are associated with mitochondrial dysfunction and can be caused by mitochondrial DNA (mtDNA) mutations, oncogenic signals, loss of tumor suppressor, and tumor tissue hypoxia. It is well established that mitochondria play central roles in energy metabolism, maintenance of redox balance, and regulation of apoptosis. However, the biochemical and molecular mechanisms that maintain high glycolysis in cancer cells (the Warburg effect) with mitochondrial dysfunction and oxidative stress remain to be determined. The major goals of this study were to establish a unique experimental system in which the mitochondrial respiratory function can be regulated as desired, and to use this system to investigate the mechanistic link between mitochondrial dysfunction and the Warburg effect along with oxidative stress in cancer cells. To achieve these goals, I have established a tetracycline-inducible system in which a dominant negative form of mitochondrial DNA polymerase y (POLGdn) expression could be regulated by tetracycline; thus controlling mitochondrial respiratory function. Using this cell system, I demonstrated that POLGdn expression resulted in mitochondrial dysfunction through decreasing mtDNA content, depletion of mtDNA encoded mRNA and protein expression. This process was mediated by TFAM proteasome degradation. Mitochondrial dysfunction mediated by POLGdn expression led to a significant increase in cellular glycolysis and oxidative stress. Surprisingly, mitochondrial dysfunction also resulted in increased NAD(P)H oxidase (NOX) enzyme activity, which was shown to be essential for maintaining high glycolysis. Chemical Inhibition of NOX activity by diphenyliodonium (DPI) preferentially impacted the survival of mitochondrial defective cells. The colon cancer HCT116-/- cells that have lost transcriptional regulation of the mitochondrial assembling enzyme SCO2, leading to compromised mitochondrial respiratory function, were found to have increased NOX activity and were highly sensitive to DPI treatment. Ovarian epithelial cells with Ras transformation also exhibited an increase in NOX gene expression and NOX enzyme activity, rendering the cells sensitive to DPI inhibition especially under hypoxic condition. These data together suggest that NOX plays a novel role in maintaining high glycolysis in cancer cells with mitochondrial defects, and that NOX may be a potential target for cancer therapy. ^

El cuerpo femenino, el sexo y la muerte en las representaciones de la política y la ciudad : Nox de Thomas Hettche, en contraste con tres relatos de la literatura argentina

Fil: Piccioni, María Laura. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

El cuerpo femenino, el sexo y la muerte en las representaciones de la política y la ciudad : Nox de Thomas Hettche, en contraste con tres relatos de la literatura argentina

Fil: Piccioni, María Laura. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Adaptación de una central térmica de carbón a la Directiva de Emisiones Industriales

El proyecto que se presenta a continuación recoge la adaptación de una Central Térmica de carbón al cumplimiento de la DIRECTIVA 2010/75/UE DEL PARLAMENTO EUROPEO Y DEL CONSEJO de 24 de noviembre de 2010 sobre las emisiones industriales. La Central sobre la que se realiza el proyecto tiene un grupo térmico de carbón suscritico refrigerado por agua, con una potencia a plena carga de 350 MWe y de 190 MWe a mínimo técnico. Genera 1 090 t/h de vapor a 540 °C y 168 kg/cm2 funcionando a plena carga. Actualmente las emisiones de NOx son de 650 mg/m3, (condiciones normales, seco, 6 % O2). El objeto del proyecto es reducir estas emisiones a un valor máximo de 200 mg/m3 en las mismas condiciones. El proyecto analiza detalladamente las condiciones actuales de operación de la instalación en cuanto a combustible utilizado, horas de funcionamiento, condiciones climáticas y producción. Se analiza así mismo, todas las técnicas disponibles en mercado para la reducción del NOx, diferenciando entre medidas primarias (actúan sobre los efectos de formación) y secundarias (limpieza de gases). Las medidas primarias ya están implementadas en la central, por tanto, el proyecto plantea la reducción con medidas secundarias. De las medidas secundarias analizadas se ha seleccionado la instalación de un Reactor de Reducción Selectiva Catalítica (Reactor SCR). Tras un análisis de los diferentes reactores y catalizadores disponibles se ha seleccionado un reactor de configuración High-dust, una disposición de catalizador en 3 capas más 1, cuyos componentes están basados en óxidos metálicos (TiO2, V2O5, WO3) y estructura laminar. Se ha buscado la instalación del reactor para operar a una temperatura inferior a 450 °C. Como agente reductor se ha seleccionado NH3 a una dilución del 24,5 %. El proyecto recoge también el diseño de todo el sistema de almacenamiento, evaporación, dilución e inyección de amoniaco. El resultado del proyecto garantiza una concentración en los gases de salida por la chimenea inferior 180 mg/m3(n) de NOx. La reducción del NOx a los límites establecidos, tienen un coste por MWh neto generado para la central, trabajando 60 % a plena carga y 40 % a mínimo técnico y una amortización de 10 años, de 4,10 €/MWh. ABSTRACT The following project shows the compliance adjustment of a coal-fired power station to the 2010/75/EU Directive of the European Parliament and Council 24th November 2010 on industrial emissions. The project is based on a power station with a subcritical thermal coal unit, cooled with water, with a maximum power of 350 MWe and a technical minimum of 190 MWe. It produces 1 090 t/h of steam at 540 ° C and 168 kg/cm2 operating under full load. Currently, NOx emissions are 650 mg / m3 (normal conditions, dry, 6% O2). The project aims to reduce these emissions to a maximum value of 200 mg / m3 under the same conditions. The project analyses in detail the current operating conditions of the system in terms of fuel used, hours of operation, climatic conditions and production. In addition, it also analyses every available technique of NOx reduction on the market, distinguishing between primary (acting on the effects of formation) and secondary measures (gas cleaning). Primary measures are already implemented in the plant, thus proposing reduction with secondary measures. Among the secondary measures analyzed, it has been selected to install a Selective Catalytic Reduction Reactor (SCR Reactor). Having researched the different reactors and catalysts available, for the reactor has been selected High-dust configuration, an arrangement of catalyst in 3 layers plus 1, whose components are based on metal oxides (TiO2, V2O5, WO3) and laminar structure. The reactor has been sought facility to operate at a temperature below 450 ° C. NH3 diluted to 24,5 % has been selected as reducing agent. The project also includes the design of the entire storage system, evaporation, dilution and ammonia injection. The results of the project ensure a gas concentration in the lower chimney exit below 180 mg / m3(n) NOx. The reduction of NOx to the established limits has a cost per net MWh generated in the plant, working at 60% of full load and at 40% of technical minimum, with an amortization of 10 years, 4,10 € / MWh.

Behavior of different soot combustion catalysts under NOx/O2. Importance of the catalyst–soot contact

Four different catalysts (Pt/Al2O3, Ce0.8Zr0.2O2, PrO2−x and SrTiCuO3) have been investigated on a laboratory scale to evaluate their potential as diesel soot combustion catalysts under different experimental conditions, which simulate the situation found in a continuous regeneration technology trap (dual-bed configuration of catalyst and soot) or a catalyst-coated filter system (single-bed configuration, both catalyst and soot particles mixed under loose-contact mode). Under dual-bed configuration, the behavior of the catalysts towards soot combustion are very similar, despite the differences observed in the NO2 production profiles. However, under single-bed configuration, there are important differences in the soot combustion activities and in the NO2 slip profiles. The configurations chosen have an enormous impact on CO/(CO + CO2) ratios of combustion products as well. The most active catalyst under NOx + O2 is PrO2−x combining a high contribution of active oxygen-assisted soot combustion as well as high NO2 production activity along the catalytic bed.

Isotopic study of ceria-catalyzed soot oxidation in the presence of NOx

The ceria-catalyzed soot oxidation mechanism has been studied by a pulse technique with labeled O2 in the absence and presence of NO, using ceria–soot mixtures prepared in the loose contact mode. In the absence of soot, the ceria-catalyzed oxidation of NO to NO2 takes place with ceria oxygen and not with gas-phase O2. However, the oxygen exchange process between gas-phase O2 and ceria oxygen (to yield back O2, but with oxygen atoms coming from ceria) prevailed with regard to the ceria-catalyzed oxidation of NO to NO2. Gas-phase O2 did not react directly with soot when pulsed to a soot–ceria loose contact mixture. Instead, ceria oxygen is transferred to soot (this step does not require gas-phase molecular oxygen to be present), and gas-phase O2 fills up the vacancies created on the oxide in a further step. The transfer of oxygen between ceria and soot occurred directly in the absence of NO. However, in the presence of NO, NO2 is expected to be additionally generated by ceria oxygen oxidation, which also reacts with soot. The main reaction products of the ceria-catalyzed soot oxidation reaction with NO/O2 were CO2 and NO. Additionally, evidence of the reduction of NOx to N2 was found.

Catalytic performance of CuO/Ce0.8Zr0.2O2 loaded onto SiC-DPF in NOx-assisted combustion of diesel soot

This work presents a comparative study between the catalytic performance of the 2% CuO/ceria-zirconia powder catalyst and the same catalyst supported on silicon carbide DPF (Diesel Particulate Filter) towards NO oxidation reaction and soot combustion reaction. The ceria-zirconia catalyst was prepared by the co-precipitation method and 2 wt% copper was incorporated by the incipient wetness impregnation method. The catalyst was incorporated onto the ceramic support using a simple and organic solvent-free procedure by a simply dipping the DPF into an aqueous solution of the catalyst. The powder catalyst has been characterized using N2 adsorption at −196 °C, XRD and Raman Spectroscopy; whereas the catalytic coating morphology has been evaluated by SEM and the mechanical stability by an adherence test. Both catalyst configurations were tested for NO oxidation to NO2 and for soot combustion under NOx/O2. The results revealed that incorporation of the very active copper/ceria-zirconia catalyst onto SiC-DPF has been successfully achieved by a simple coating procedure. Furthermore, the catalytic coating has shown suitable mechanical, chemical and thermal stability. A satisfactory catalytic performance of the catalytic-coated filter was reached towards the NO oxidation reaction. Moreover, it was proved that the catalytic coating is stable and the corresponding coated DPF can be reused for several cycles of NO oxidation without a significant decrease in its activity. Finally, it was verified that the loose-contact mode is a good choice to simulate the catalytic performance of this active phase in a real diesel particulate filter.

Electrospinning of silica sub-microtubes mats with platinum nanoparticles for NO catalytic reduction

Silica sub-microtubes loaded with platinum nanoparticles have been prepared in flexible non-woven mats using co-axial electrospinning technique. A partially gelated sol made from tetraethyl orthosilicate was used as the silica precursor, and oil was used as the sacrificial template for the hollow channel generation. Platinum has been supported on the wall of the tubes just adding the metallic precursor to the sol–gel, thus obtaining the supported catalyst by one-pot method. The silica tubes have a high aspect ratio with external/internal diameters of 400/200 nm and well-dispersed platinum nanoparticles of around 2 nm. This catalyst showed a high NO conversion with very high selectivity to N2 at mild conditions in the presence of excess oxygen when using C3H6 as reducing agent. This relevant result reveals the potential of this technique to produce nanostructured catalysts onto easy to handle conformations.

NOx storage and reduction over copper-based catalysts. Part 2: Ce0.8M0.2Oδ supports (M = Zr, La, Ce, Pr or Nd)

5% copper catalysts with Ce0.8M0.2Oδ supports (M = Zr, La, Ce, Pr or Nd) have been studied by rapid-scan operando DRIFTS for NOx Storage and Reduction (NSR) with high frequency (30 s) CO, H2 and 50%CO + 50%H2 micropulses. In the absence of reductant pulses, below 200–250 °C NOx was stored on the catalysts as nitrite and nitro groups, and above this temperature nitrates were the main species identified. The thermal stability of the NOx species stored on the catalysts depended on the acid/basic character of the dopant (M more acidic = NOx stored less stable ⇒ Zr4+ < none < Nd3+ < Pr3+ < La3+ ⇐ M more basic = NOx stored more stable). Catalysts regeneration was more efficient with H2 than with CO, and the CO + H2 mixture presented an intermediate behavior, but with smaller differences among the series of catalyst than observed using CO alone. N2 is the main NOx reduction product upon H2 regeneration. The highest NOx removal in NSR experiments performed at 400 °C with CO + H2 pulses was achieved with the catalyst with the most basic dopant (CuO/Ce0.8La0.2Oδ) while the poorest performing catalyst was that with the most acidic dopant (CuO/Ce0.8Zr0.2Oδ). The poor performance of CuO/Ce0.8Zr0.2Oδ in NSR experiments with CO pulses was attributed to its lower oxidation capacity compared to the other catalysts.

Sourcebook, NOx control technology data /

Mode of access: Internet.

Effects of coal-bound chlorine on furnace-wall corrosion under low-NOx conditions /

"5/02"--Colophon.